DNA and RNA binding proteins (DRBPs) are a broad class of molecules that regulate numerous cellular processes across all living organisms, creating intricate dynamic multilevel networks to control nucleotide metabolism and gene expression. These interactions are highly regulated, and dysregulation contributes to the development of a variety of diseases, including cancer. An increasing number of proteins with DNA and/or RNA binding activities have been identified in recent years, and it is important to understand how their activities are related to the molecular mechanisms of cancer. In addition, many of these proteins have overlapping functions, and it is therefore essential to analyze not only the loss of function of individual factors, but also to group abnormalities into specific types of activities in regard to particular cancer types. In this review, we summarize the classes of DNA-binding, RNA-binding, and DRBPs, drawing particular attention to the similarities and differences between these protein classes. We also perform a cross-search analysis of relevant protein databases, together with our own pipeline, to identify DRBPs involved in cancer. We discuss the most common DRBPs and how they are related to specific cancers, reviewing their biochemical, molecular biological, and cellular properties to highlight their functions and potential as targets for treatment.

Department of Medical Biosciences Umea University 90187 Umea Sweden

Research Centre for Applied Molecular Oncology Zluty Kopec 7 656 53 Brno Czech Republic

Zobrazit více v PubMed

Cozzolino F., Iacobucci I., Monaco V., Monti M. Protein–DNA/RNA Interactions: An Overview of Investigation Methods in the -Omics Era. J. Proteome Res. 2021;20:3018–3030. doi: 10.1021/acs.jproteome.1c00074. PubMed DOI PMC

Mirabile G., Campo C., Ettari R., Aguennouz M.H., Musolino C., Allegra A. New Insights into Cold Shock Proteins Effects in Human Cancer: Correlation with Susceptibility, Prognosis and Therapeutical Perspectives. Curr. Med. Chem. 2022 doi: 10.2174/0929867329666220601142924. PubMed DOI

Hudson W., Ortlund E. The structure, function and evolution of proteins that bind DNA and RNA. Nat. Rev. Mol. Cell Biol. 2014;15:749–760. doi: 10.1038/nrm3884. PubMed DOI PMC

Steitz T.A. Structural studies of protein–nucleic acid interaction: The sources of sequence-specific binding. Q. Rev. Biophys. 1990;23:205–280. doi: 10.1017/S0033583500005552. PubMed DOI

Krajewska W.M. Regulation of transcription in eukaryotes by DNA-binding proteins. Int. J. Biochem. 1992;24:1885–1898. doi: 10.1016/0020-711X(92)90284-8. PubMed DOI

Pabo C.O., Sauer R.T. Transcription Factors: Structural Families and Principles of DNA Recognition. Annu. Rev. Biochem. 1992;61:1053–1095. doi: 10.1146/annurev.bi.61.070192.005201. PubMed DOI

Struhl K. Helix-turn-helix, zinc-finger, and leucine-zipper motifs for eukaryotic transcriptional regulatory proteins. Trends Biochem. Sci. 1989;14:137–140. doi: 10.1016/0968-0004(89)90145-X. PubMed DOI

Rosinski J.A., Atchley W.R. Molecular Evolution of Helix–Turn–Helix Proteins. J. Mol. Evol. 1999;49:301–309. doi: 10.1007/PL00006552. PubMed DOI

Pabo C.O., Sauer R.T. Protein-Dna Recognition. Annu. Rev. Biochem. 1984;53:293–321. doi: 10.1146/annurev.bi.53.070184.001453. PubMed DOI

Brennan R.G., Matthews B.W. The helix-turn-helix DNA binding motif. J. Biol. Chem. 1989;264:1903–1906. doi: 10.1016/S0021-9258(18)94115-3. PubMed DOI

Otting G., Qian Y.Q., Billeter M., Müller M., Affolter M., Gehring W.J., Wüthrich K. Protein-DNA contacts in the structure of a homeodomain-DNA complex determined by nuclear magnetic resonance spectroscopy in solution. EMBO J. 1990;9:3085–3092. doi: 10.1002/j.1460-2075.1990.tb07505.x. PubMed DOI PMC

Aravind L., Anantharaman V., Balaji S., Babu M., Iyer L. The many faces of the helix-turn-helix domain: Transcription regulation and beyond. FEMS Microbiol. Rev. 2005;29:231–262. doi: 10.1016/j.femsre.2004.12.008. PubMed DOI

Morgenstern B., Atchley W.R. Evolution of bHLH transcription factors: Modular evolution by domain shuffling? Mol. Biol. Evol. 1999;16:1654–1663. doi: 10.1093/oxfordjournals.molbev.a026079. PubMed DOI

Atchley W.R., Fitch W.M. A natural classification of the basic helix–loop–helix class of transcription factors. Proc. Natl. Acad. Sci. USA. 1997;94:5172–5176. doi: 10.1073/pnas.94.10.5172. PubMed DOI PMC

Ledent V., Paquet O., Vervoort M. Phylogenetic analysis of the human basic helix-loop-helix proteins. Genome Biol. 2002;3:RESEARCH0030. doi: 10.1186/gb-2002-3-6-research0030. PubMed DOI PMC

Murre C., Bain G., van Dijk M.A., Engel I., Furnari B.A., Massari M.E., Matthews J.R., Quong M.W., Rivera R.R., Stuiver M.H. Structure and function of helix-loop-helix proteins. Biochim. Biophys. Acta BBA-Gene Struct. Expr. 1994;1218:129–135. doi: 10.1016/0167-4781(94)90001-9. PubMed DOI

Atchley W.R., Terhalle W., Dress A. Positional Dependence, Cliques, and Predictive Motifs in the bHLH Protein Domain. J. Mol. Evol. 1999;48:501–516. doi: 10.1007/PL00006494. PubMed DOI

Vinson C.R., Garcia K.C. Molecular model for DNA recognition by the family of basic-helix-loop-helix-zipper proteins. New Biol. 1992;4:396–403. PubMed

Hjalt T. Basic Helix–Loop–Helix Proteins Expressed During Early Embryonic Organogenesis. Int. Rev. Cytol. 2004;236:251–280. doi: 10.1016/s0074-7696(04)36006-7. PubMed DOI

Raumann B.E., Brown B.M., Sauer R. Major groove DNA recognition by β-sheets: The ribbon-helix-helix family of gene regulatory proteins. Curr. Opin. Struct. Biol. 1994;4:36–43. doi: 10.1016/S0959-440X(94)90057-4. DOI

Connolly K.M., Ilangovan U., Wojciak J.M., Iwahara M., Clubb R.T. Major Groove Recognition by Three-stranded β-Sheets: Affinity Determinants and Conserved Structural Features. J. Mol. Biol. 2000;300:841–856. doi: 10.1006/jmbi.2000.3888. PubMed DOI

Landschulz W.H., Johnson P.F., McKnight S.L. The Leucine Zipper: A Hypothetical Structure Common to a New Class of DNA Binding Proteins. Science. 1988;240:1759–1764. doi: 10.1126/science.3289117. PubMed DOI

Kouzarides T., Ziff E. The role of the leucine zipper in the fos–jun interaction. Nature. 1988;336:646–651. doi: 10.1038/336646a0. PubMed DOI

Bustin M. Regulation of DNA-Dependent Activities by the Functional Motifs of the High-Mobility-Group Chromosomal Proteins. Mol. Cell. Biol. 1999;19:5237–5246. doi: 10.1128/MCB.19.8.5237. PubMed DOI PMC

Agresti A., Bianchi M.E. HMGB proteins and gene expression. Curr. Opin. Genet. Dev. 2003;13:170–178. doi: 10.1016/S0959-437X(03)00023-6. PubMed DOI

Štros M. HMGB proteins: Interactions with DNA and chromatin. Biochim. Biophys. Acta. 2010;1799:101–113. doi: 10.1016/j.bbagrm.2009.09.008. PubMed DOI

Gerlitz G., Hock R., Ueda T., Bustin M. The Dynamics of HMG Protein-Chromatin Interactions in Living Cells. Biochem. Cell Biol. 2009;87:127–137. doi: 10.1139/O08-110. PubMed DOI PMC

Ueda T., Yoshida M. HMGB proteins and transcriptional regulation. Biochim. Biophys. Acta. 2010;1799:114–118. doi: 10.1016/j.bbagrm.2009.11.005. PubMed DOI

Hentze M., Castello A., Schwarzl T., Preiss T. A brave new world of RNA-binding proteins. Nat. Rev. Mol. Cell Biol. 2018;19:327–341. doi: 10.1038/nrm.2017.130. PubMed DOI

Hoffman M.M., Khrapov M.A., Cox J.C., Yao J., Tong L., Ellington A.D. AANT: The Amino Acid-Nucleotide Interaction Database. Nucleic Acids Res. 2004;32:D174–D181. doi: 10.1093/nar/gkh128. PubMed DOI PMC

Jones S., Daley D.T., Luscombe N.M., Berman H.M., Thornton J.M. Protein-RNA interactions: A structural analysis. Nucleic Acids Res. 2001;29:943–954. doi: 10.1093/nar/29.4.943. PubMed DOI PMC

Corley M., Burns M.C., Yeo G.W. How RNA-Binding Proteins Interact with RNA: Molecules and Mechanisms. Mol. Cell. 2020;78:9–29. doi: 10.1016/j.molcel.2020.03.011. PubMed DOI PMC

Wilson K., Kellie J.L., Wetmore S.D. DNA–protein π-interactions in nature: Abundance, structure, composition and strength of contacts between aromatic amino acids and DNA nucleobases or deoxyribose sugar. Nucleic Acids Res. 2014;42:6726–6741. doi: 10.1093/nar/gku269. PubMed DOI PMC

Draper D.E. Themes in RNA-protein recognition. J. Mol. Biol. 1999;293:255–270. doi: 10.1006/jmbi.1999.2991. PubMed DOI

Cléry A., Blatter M., Allain F.H.-T. RNA recognition motifs: Boring? Not quite. Curr. Opin. Struct. Biol. 2008;18:290–298. doi: 10.1016/j.sbi.2008.04.002. PubMed DOI

Masliah G., Barraud P., Allain F.H.-T. RNA recognition by double-stranded RNA binding domains: A matter of shape and sequence. Cell Mol. Life Sci. 2012;70:1875–1895. doi: 10.1007/s00018-012-1119-x. PubMed DOI PMC

Vuković L., Koh H.R., Myong S., Schulten K. Substrate Recognition and Specificity of Double-Stranded RNA Binding Proteins. Biochemistry. 2014;53:3457–3466. doi: 10.1021/bi500352s. PubMed DOI PMC

Edwards T.A. Bespoke RNA recognition by Pumilios. Biochem. Soc. Trans. 2015;43:801–806. doi: 10.1042/BST20150072. PubMed DOI

Wang M., Ogé L., Perez-Garcia M.-D., Hamama L., Sakr S. The PUF Protein Family: Overview on PUF RNA Targets, Biological Functions, and Post Transcriptional Regulation. Int. J. Mol. Sci. 2018;19:E410. doi: 10.3390/ijms19020410. PubMed DOI PMC

Zhao Y.-Y., Mao M.-W., Zhang W.-J., Wang J., Li H., Yang Y., Wang Z., Wu J.-W. Expanding RNA binding specificity and affinity of engineered PUF domains. Nucleic Acids Res. 2018;46:4771–4782. doi: 10.1093/nar/gky134. PubMed DOI PMC

Mitchell S.F., Parker R. Principles and Properties of Eukaryotic mRNPs. Mol. Cell. 2014;54:547–558. doi: 10.1016/j.molcel.2014.04.033. PubMed DOI

Schröder K., Graumann P., Schnuchel A., Holak T.A., Marahiel M.A. Mutational analysis of the putative nucleic acid-binding surface of the cold-shock domain, CspB, revealed an essential role of aromatic and basic residues in binding of single-stranded DNA containing the Y-box motif. Mol. Microbiol. 1995;16:699–708. doi: 10.1111/j.1365-2958.1995.tb02431.x. PubMed DOI

Heinemann U., Roske Y. Cold-Shock Domains—Abundance, Structure, Properties, and Nucleic-Acid Binding. Cancers. 2021;13:190. doi: 10.3390/cancers13020190. PubMed DOI PMC

Yang X.-J., Zhu H., Mu S.-R., Wei W.-J., Yuan X., Wang M., Liu Y., Hui J., Huang Y. Crystal structure of a Y-box binding protein 1 (YB-1)–RNA complex reveals key features and residues interacting with RNA. J. Biol. Chem. 2019;294:10998–11010. doi: 10.1074/jbc.RA119.007545. PubMed DOI PMC

Budkina K.S., Zlobin N.E., Kononova S.V., Ovchinnikov L.P., Babakov A.V. Cold Shock Domain Proteins: Structure and Interaction with Nucleic Acids. Biochemistry. 2020;85:1–19. doi: 10.1134/S0006297920140011. PubMed DOI

Miller J., McLachlan A., Klug A. Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J. 1985;4:1609–1614. doi: 10.1002/j.1460-2075.1985.tb03825.x. PubMed DOI PMC

Clemens K.R., Wolf V., McBryant S.J., Zhang P., Liao X., Wright P.E., Gottesfeld J.M. Molecular Basis for Specific Recognition of Both RNA and DNA by a Zinc Finger Protein. Science. 1993;260:530–533. doi: 10.1126/science.8475383. PubMed DOI

Klug A. The discovery of zinc fingers and their development for practical applications in gene regulation and genome manipulation. Q. Rev. Biophys. 2010;43:1–21. doi: 10.1017/S0033583510000089. PubMed DOI

Zilliacus J., Wright A., Carlstedt-Duke J., Gustafsson J. Structural determinants of DNA-binding specificity by steroid receptors. Mol. Endocrinol. 1995;9:389–400. doi: 10.1210/mend.9.4.7659083. PubMed DOI

Siomi H., Matunis M., Michael W.M., Dreyfuss G. The pre-mRNA binding K protein contains a novel evolutionary conserved motif. Nucleic Acids Res. 1993;21:1193–1198. doi: 10.1093/nar/21.5.1193. PubMed DOI PMC

Musco G., Stier G., Joseph C., Morelli M.A.C., Nilges M., Gibson T.J., Pastore A. Three-Dimensional Structure and Stability of the KH Domain: Molecular Insights into the Fragile X Syndrome. Cell. 1996;85:237–245. doi: 10.1016/S0092-8674(00)81100-9. PubMed DOI

Grishin N.V. KH domain: One motif, two folds. Nucleic Acids Res. 2001;29:638–643. doi: 10.1093/nar/29.3.638. PubMed DOI PMC

Valverde R., Edwards L., Regan L. Structure and function of KH domains. FEBS J. 2008;275:2712–2726. doi: 10.1111/j.1742-4658.2008.06411.x. PubMed DOI

Nicastro G., Taylor I.A., Ramos A. KH–RNA interactions: Back in the groove. Curr. Opin. Struct. Biol. 2015;30:63–70. doi: 10.1016/j.sbi.2015.01.002. PubMed DOI

The UniProt Consortium UniProt: The universal protein knowledgebase in 2021. Nucleic Acids Res. 2021;49:D480–D489. doi: 10.1093/nar/gkaa1100. PubMed DOI PMC

Ashburner M., Ball C.A., Blake J.A., Botstein D., Butler H., Cherry J.M., Davis A.P., Dolinski K., Dwight S.S., Eppig J.T., et al. Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 2000;25:25–29. doi: 10.1038/75556. PubMed DOI PMC

Leung R.W.T., Jiang X., Chu K.H., Qin J. ENPD—A Database of Eukaryotic Nucleic Acid Binding Proteins: Linking Gene Regulations to Proteins. Nucleic Acids Res. 2018;47:D322–D329. doi: 10.1093/nar/gky1112. PubMed DOI PMC

Cook K.B., Kazan H., Zuberi K., Morris Q., Hughes T.R. RBPDB: A database of RNA-binding specificities. Nucleic Acids Res. 2010;39:D301–D308. doi: 10.1093/nar/gkq1069. PubMed DOI PMC

Huntley R.P., Sawford T., Mutowo P., Shypitsyna A., Bonilla C., Martin M.-J., O’Donovan C. The GOA database: Gene Ontology annotation updates for 2015. Nucleic Acids Res. 2014;43:D1057–D1063. doi: 10.1093/nar/gku1113. PubMed DOI PMC

Binns D., Dimmer E., Huntley R., Barrell D., O’Donovan C., Apweiler R. QuickGO: A web-based tool for Gene Ontology searching. Bioinformatics. 2009;25:3045–3046. doi: 10.1093/bioinformatics/btp536. PubMed DOI PMC

Cerami E., Gao J., Dogrusoz U., Gross B.E., Sumer S.O., Aksoy B.A., Jacobsen A., Byrne C.J., Heuer M.L., Larsson E., et al. The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401–404. doi: 10.1158/2159-8290.CD-12-0095. PubMed DOI PMC

Gao J., Aksoy B.A., Dogrusoz U., Dresdner G., Gross B.E., Sumer S.O., Sun Y., Jacobsen A., Sinha R., Larsson E., et al. Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal. Sci. Signal. 2013;6:pl1. doi: 10.1126/scisignal.2004088. PubMed DOI PMC

Szklarczyk D., Gable A.L., Lyon D., Junge A., Wyder S., Huerta-Cepas J., Simonovic M., Doncheva N.T., Morris J.H., Bork P., et al. STRING v11: Protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47:D607–D613. doi: 10.1093/nar/gky1131. PubMed DOI PMC

Jankowsky E. RNA helicases at work: Binding and rearranging. Trends Biochem. Sci. 2011;36:19–29. doi: 10.1016/j.tibs.2010.07.008. PubMed DOI PMC

Fullam A., Schröder M. DExD/H-box RNA helicases as mediators of anti-viral innate immunity and essential host factors for viral replication. Biochim. Biophys. Acta. 2013;1829:854–865. doi: 10.1016/j.bbagrm.2013.03.012. PubMed DOI PMC

Cruciat C.-M., Dolde C., de Groot R.E.A., Ohkawara B., Reinhard C., Korswagen H.C., Niehrs C. RNA Helicase DDX3 Is a Regulatory Subunit of Casein Kinase 1 in Wnt–β-Catenin Signaling. Science. 2013;339:1436–1441. doi: 10.1126/science.1231499. PubMed DOI

Kasim V., Wu S., Taira K., Miyagishi M. Determination of the Role of DDX3 a Factor Involved in Mammalian RNAi Pathway Using an shRNA-Expression Library. PLoS ONE. 2013;8:e59445. doi: 10.1371/journal.pone.0059445. PubMed DOI PMC

Sharma D., Jankowsky E. The Ded1/DDX3 subfamily of DEAD-box RNA helicases. Crit. Rev. Biochem. Mol. Biol. 2014;49:343–360. doi: 10.3109/10409238.2014.931339. PubMed DOI

Kukhanova M.K., Karpenko I.L., Ivanov A.V. DEAD-box RNA Helicase DDX3: Functional Properties and Development of DDX3 Inhibitors as Antiviral and Anticancer Drugs. Molecules. 2020;25:E1015. doi: 10.3390/molecules25041015. PubMed DOI PMC

Miyashita M., Oshiumi H., Matsumoto M., Seya T. DDX60, a DEXD/H Box Helicase, Is a Novel Antiviral Factor Promoting RIG-I-Like Receptor-Mediated Signaling. Mol. Cell. Biol. 2011;31:3802–3819. doi: 10.1128/MCB.01368-10. PubMed DOI PMC

Xin D., Liu J., Gu J., Ji Y., Jin J., Sun L., Tai Q., Cao J., Tian Y., Qin H., et al. Low Expression of DDX60 Gene Might Associate with the Radiosensitivity for Patients with Breast Cancer. J. Oncol. 2020;2020:8309492. doi: 10.1155/2020/8309492. PubMed DOI PMC

Fu T.-Y., Wu C.-N., Sie H.-C., Cheng J.-T., Lin Y.-S., Liou H.-H., Tseng Y.-K., Shu C.-W., Tsai K.-W., Yen L.-M., et al. Subsite-specific association of DEAD box RNA helicase DDX60 with the development and prognosis of oral squamous cell carcinoma. Oncotarget. 2016;7:85097–85108. doi: 10.18632/oncotarget.13197. PubMed DOI PMC

Zhang J., Fu M., Zhang M., Zhang J., Du Z., Zhang H., Hua W., Mao Y. DDX60 Is Associated With Glioma Malignancy and Serves as a Potential Immunotherapy Biomarker. Front. Oncol. 2021;11:665360. doi: 10.3389/fonc.2021.665360. PubMed DOI PMC

Shen L., Pelletier J. General and Target-Specific DExD/H RNA Helicases in Eukaryotic Translation Initiation. Int. J. Mol. Sci. 2020;21:4402. doi: 10.3390/ijms21124402. PubMed DOI PMC

Hossain K.A., Jurkowski M., Czub J., Kogut M. Mechanism of recognition of parallel G-quadruplexes by DEAH/RHAU helicase DHX36 explored by molecular dynamics simulations. Comput. Struct. Biotechnol. J. 2021;19:2526–2536. doi: 10.1016/j.csbj.2021.04.039. PubMed DOI PMC

Manojlovic Z., Stefanovic B. A novel role of RNA helicase A in regulation of translation of type I collagen mRNAs. RNA. 2011;18:321–334. doi: 10.1261/rna.030288.111. PubMed DOI PMC

Halaby M.-J., Li Y., Harris B.R., Jiang S., Miskimins W.K., Cleary M.P., Yang D.-Q. Translational Control Protein 80 Stimulates IRES-Mediated Translation of p53 mRNA in Response to DNA Damage. BioMed Res. Int. 2015;2015:708158. doi: 10.1155/2015/708158. PubMed DOI PMC

Wu W., Qu Y., Yu S., Wang S., Yin Y., Liu Q., Meng C., Liao Y., Rehman Z.U., Tan L., et al. Caspase-Dependent Cleavage of DDX21 Suppresses Host Innate Immunity. mBio. 2021;12:e0100521. doi: 10.1128/mBio.01005-21. PubMed DOI PMC

Briard B., Place D., Kanneganti T.-D. DNA Sensing in the Innate Immune Response. Physiology. 2020;35:112–124. doi: 10.1152/physiol.00022.2019. PubMed DOI PMC

Booy E.P., Howard R., Marushchak O., Ariyo E.O., Meier M., Novakowski S.K., Deo S.R., Dzananovic E., Stetefeld J., McKenna S.A. The RNA helicase RHAU (DHX36) suppresses expression of the transcription factor PITX1. Nucleic Acids Res. 2013;42:3346–3361. doi: 10.1093/nar/gkt1340. PubMed DOI PMC

Newman M., Sfaxi R., Saha A., Monchaud D., Teulade-Fichou M.-P., Vagner S. The G-Quadruplex-Specific RNA Helicase DHX36 Regulates p53 Pre-mRNA 3′-End Processing Following UV-Induced DNA Damage. J. Mol. Biol. 2017;429:3121–3131. doi: 10.1016/j.jmb.2016.11.033. PubMed DOI

He L., Liu Y., Lai W., Tian H., Chen L., Xie L., Liu Z. DNA sensors, crucial receptors to resist pathogens, are deregulated in colorectal cancer and associated with initiation and progression of the disease. J. Cancer. 2020;11:893–905. doi: 10.7150/jca.34188. PubMed DOI PMC

Yan X., Chang J., Sun R., Meng X., Wang W., Zeng L., Liu B., Li W., Yan X., Huang C., et al. DHX9 Inhibits Epitheli-al-Mesenchymal Transition in Human Lung Adenocarcinoma Cells by Regulating STAT3. Am. J. Transl. Res. 2019;11:4881–4894. PubMed PMC

Cui Y., Li Z., Cao J., Lane J., Birkin E., Dong X., Zhang L., Jiang W.G. The G4 Resolvase DHX36 Possesses a Prognosis Significance and Exerts Tumour Suppressing Function Through Multiple Causal Regulations in Non-Small Cell Lung Cancer. Front. Oncol. 2021;11:655757. doi: 10.3389/fonc.2021.655757. PubMed DOI PMC

Karatas O.F., Capik O., Barlak N., Karatas E.A. Comprehensive in silico analysis for identification of novel candidate target genes, including DHX36, OPA1, and SENP2, located on chromosome 3q in head and neck cancers. Head Neck. 2021;43:288–302. doi: 10.1002/hed.26493. PubMed DOI

Torchy M.P., Hamiche A., Klaholz B.P. Structure and function insights into the NuRD chromatin remodeling complex. Cell Mol. Life Sci. 2015;72:2491–2507. doi: 10.1007/s00018-015-1880-8. PubMed DOI PMC

Xiao R., Chen J.-Y., Liang Z., Luo D., Chen G., Lu Z.J., Chen Y., Zhou B., Li H., Du X., et al. Pervasive Chromatin-RNA Binding Protein Interactions Enable RNA-Based Regulation of Transcription. Cell. 2019;178:107–121.e18. doi: 10.1016/j.cell.2019.06.001. PubMed DOI PMC

Blok L.S., The DDD Study. Rousseau J., Twist J., Ehresmann S., Takaku M., Venselaar H., Rodan L.H., Nowak C.B., Douglas J., et al. CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language. Nat. Commun. 2018;9:4619. doi: 10.1038/s41467-018-06014-6. PubMed DOI PMC

Li W., Mills A.A. Architects of the genome: CHD dysfunction in cancer, developmental disorders and neurological syndromes. Epigenomics. 2014;6:381–395. doi: 10.2217/epi.14.31. PubMed DOI PMC

Alendar A., Berns A. Sentinels of chromatin: Chromodomain helicase DNA-binding proteins in development and disease. Genes Dev. 2021;35:1403–1430. doi: 10.1101/gad.348897.121. PubMed DOI PMC

Fiorini F., Bagchi D., Le Hir H., Croquette V. Human Upf1 is a highly processive RNA helicase and translocase with RNP remodelling activities. Nat. Commun. 2015;6:7581. doi: 10.1038/ncomms8581. PubMed DOI PMC

Chamieh H., Ballut L., Bonneau F., Le Hir H. NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity. Nat. Struct. Mol. Biol. 2007;15:85–93. doi: 10.1038/nsmb1330. PubMed DOI

Chakrabarti S., Jayachandran U., Bonneau F., Fiorini F., Basquin C., Domcke S., Le Hir H., Conti E. Molecular Mechanisms for the RNA-Dependent ATPase Activity of Upf1 and Its Regulation by Upf2. Mol. Cell. 2011;41:693–703. doi: 10.1016/j.molcel.2011.02.010. PubMed DOI

Fiorini F., Boudvillain M., Le Hir H. Tight intramolecular regulation of the human Upf1 helicase by its N- and C-terminal domains. Nucleic Acids Res. 2012;41:2404–2415. doi: 10.1093/nar/gks1320. PubMed DOI PMC

Kalathiya U., Padariya M., Pawlicka K., Verma C.S., Houston D., Hupp T.R., Alfaro J.A. Insights into the Effects of Cancer Associated Mutations at the UPF2 and ATP-Binding Sites of NMD Master Regulator: UPF1. Int. J. Mol. Sci. 2019;20:E5644. doi: 10.3390/ijms20225644. PubMed DOI PMC

Azzalin C.M., Lingner J. The Human RNA Surveillance Factor UPF1 Is Required for S Phase Progression and Genome Stability. Curr. Biol. 2006;16:433–439. doi: 10.1016/j.cub.2006.01.018. PubMed DOI

Chawla R., Redon S., Raftopoulou C., Wischnewski H., Gagos S., Azzalin C.M. Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication. EMBO J. 2011;30:4047–4058. doi: 10.1038/emboj.2011.280. PubMed DOI PMC

Liu C., Karam R., Zhou Y., Su F., Ji Y., Li G., Xu G., Lu L., Wang C., Song M., et al. The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma. Nat. Med. 2014;20:596–598. doi: 10.1038/nm.3548. PubMed DOI PMC

Pei C.-L., Fei K.-L., Yuan X.-Y., Gong X.-J. LncRNA DANCR Aggravates the Progression of Ovarian Cancer by Down-regulating UPF1. Eur. Rev. Med. Pharmacol. Sci. 2019;23:10657–10663. doi: 10.26355/eurrev_201912_19763. PubMed DOI

Lv Z.-H., Wang Z.-Y., Li Z.-Y. LncRNA PVT1 aggravates the progression of glioma via downregulating UPF1. Eur. Rev. Med. Pharmacol. Sci. 2019;23:8956–8963. PubMed

Chang L., Yuan Y., Li C., Guo T., Qi H., Xiao Y., Dong X., Liu Z., Liu Q. Upregulation of SNHG6 regulates ZEB1 expression by competitively binding miR-101-3p and interacting with UPF1 in hepatocellular carcinoma. Cancer Lett. 2016;383:183–194. doi: 10.1016/j.canlet.2016.09.034. PubMed DOI

Zhou Y., Li Y., Wang N., Li X., Zheng J., Ge L. UPF1 inhibits the hepatocellular carcinoma progression by targeting long non-coding RNA UCA1. Sci. Rep. 2019;9:6652. doi: 10.1038/s41598-019-43148-z. PubMed DOI PMC

Cao L., Qi L., Zhang L., Song W., Yu Y., Xu C., Li L., Guo Y., Yang L., Liu C., et al. Human nonsense-mediated RNA decay regulates EMT by targeting the TGF-ß signaling pathway in lung adenocarcinoma. Cancer Lett. 2017;403:246–259. doi: 10.1016/j.canlet.2017.06.021. PubMed DOI

Hafner A., Bulyk M.L., Jambhekar A., Lahav G. The multiple mechanisms that regulate p53 activity and cell fate. Nat. Rev. Mol. Cell Biol. 2019;20:199–210. doi: 10.1038/s41580-019-0110-x. PubMed DOI

Olivares-Illana V., Fåhraeus R. p53 isoforms gain functions. Oncogene. 2010;29:5113–5119. doi: 10.1038/onc.2010.266. PubMed DOI

Ozaki T., Nakagawara A. Role of p53 in Cell Death and Human Cancers. Cancers. 2011;3:994–1013. doi: 10.3390/cancers3010994. PubMed DOI PMC

Walker K.K., Levine A.J. Identification of a novel p53 functional domain that is necessary for efficient growth suppression. Proc. Natl. Acad. Sci. USA. 1996;93:15335–15340. doi: 10.1073/pnas.93.26.15335. PubMed DOI PMC

Pavletich N.P., Chambers K.A., Pabo C.O. The DNA-binding domain of p53 contains the four conserved regions and the major mutation hot spots. Genes Dev. 1993;7:2556–2564. doi: 10.1101/gad.7.12b.2556. PubMed DOI

Clore G.M., Ernst J., Clubb R., Omichinski J.G., Kennedy W.P., Sakaguchi K., Appella E., Gronenborn A.M. Refined solution structure of the oligomerization domain of the tumour suppressor p53. Nat. Struct. Mol. Biol. 1995;2:321–333. doi: 10.1038/nsb0495-321. PubMed DOI

Mosner J., Mummenbrauer T., Bauer C., Sczakiel G., Grosse F., Deppert W. Negative feedback regulation of wild-type p53 biosynthesis. EMBO J. 1995;14:4442–4449. doi: 10.1002/j.1460-2075.1995.tb00123.x. PubMed DOI PMC

Tournillon A.-S., López I., Malbert-Colas L., Findakly S., Naski N., Olivares-Illana V., Karakostis K., Vojtesek B., Nylander K., Fåhraeus R. p53 binds the mdmx mRNA and controls its translation. Oncogene. 2016;36:723–730. doi: 10.1038/onc.2016.236. PubMed DOI

López I., Tournillon A.-S., Martins R.P., Karakostis K., Malbert-Colas L., Nylander K., Fåhraeus R. p53-mediated suppression of BiP triggers BIK-induced apoptosis during prolonged endoplasmic reticulum stress. Cell Death Differ. 2017;24:1717–1729. doi: 10.1038/cdd.2017.96. PubMed DOI PMC

Yoshida Y., Izumi H., Torigoe T., Ishiguchi H., Yoshida T., Itoh H., Kohno K. Binding of RNA to p53 regulates its oligomerization and DNA-binding activity. Oncogene. 2004;23:4371–4379. doi: 10.1038/sj.onc.1207583. PubMed DOI

Jin T., Perry A., Jiang J., Smith P., Curry J.A., Unterholzner L., Jiang Z., Horvath G., Rathinam V.A., Johnstone R.W., et al. Structures of the HIN Domain:DNA Complexes Reveal Ligand Binding and Activation Mechanisms of the AIM2 Inflammasome and IFI16 Receptor. Immunity. 2012;36:561–571. doi: 10.1016/j.immuni.2012.02.014. PubMed DOI PMC

Ansari M.A., Singh V.V., Dutta S., Veettil M.V., Dutta D., Chikoti L., Lu J., Everly D., Chandran B. Constitutive Interferon-Inducible Protein 16-Inflammasome Activation during Epstein-Barr Virus Latency I, II, and III in B and Epithelial Cells. J. Virol. 2013;87:8606–8623. doi: 10.1128/JVI.00805-13. PubMed DOI PMC

Kerur N., Veettil M.V., Sharma-Walia N., Bottero V., Sadagopan S., Otageri P., Chandran B. IFI16 Acts as a Nuclear Pathogen Sensor to Induce the Inflammasome in Response to Kaposi Sarcoma-Associated Herpesvirus Infection. Cell Host Microbe. 2011;9:363–375. doi: 10.1016/j.chom.2011.04.008. PubMed DOI PMC

Lum K.K., Howard T.R., Pan C., Cristea I.M. Charge-Mediated Pyrin Oligomerization Nucleates Antiviral IFI16 Sensing of Herpesvirus DNA. mBio. 2019;10:e01428-19. doi: 10.1128/mBio.01428-19. PubMed DOI PMC

Hotter D., Bosso M., Jønsson K.L., Krapp C., Stürzel C.M., Das A., Littwitz-Salomon E., Berkhout B., Russ A., Wittmann S., et al. IFI16 Targets the Transcription Factor Sp1 to Suppress HIV-1 Transcription and Latency Reactivation. Cell Host Microbe. 2019;25:858–872.e13. doi: 10.1016/j.chom.2019.05.002. PubMed DOI PMC

Choubey D. DNA-responsive inflammasomes and their regulators in autoimmunity. Clin. Immunol. 2012;142:223–231. doi: 10.1016/j.clim.2011.12.007. PubMed DOI PMC

Gariano G.R., Dell’Oste V., Bronzini M., Gatti D., Luganini A., De Andrea M., Gribaudo G., Gariglio M., Landolfo S. The Intracellular DNA Sensor IFI16 Gene Acts as Restriction Factor for Human Cytomegalovirus Replication. [(accessed on 16 July 2018)];PLoS Pathog. 2012 8:e1002498. doi: 10.1371/journal.ppat.1002498. Available online: http://www.ncbi.nlm.nih.gov/pubmed/22291595. PubMed DOI PMC

Brázda V., Coufal J., Liao J.C., Arrowsmith C.H. Preferential binding of IFI16 protein to cruciform structure and superhelical DNA. Biochem. Biophys. Res. Commun. 2012;422:716–720. doi: 10.1016/j.bbrc.2012.05.065. PubMed DOI

Hároníková L., Coufal J., Kejnovská I., Jagelská E.B., Fojta M., Dvořáková P., Muller P., Vojtesek B., Brázda V. IFI16 Preferentially Binds to DNA with Quadruplex Structure and Enhances DNA Quadruplex Formation. PLoS ONE. 2016;11:e0157156. doi: 10.1371/journal.pone.0157156. PubMed DOI PMC

Jiang Z., Wei F., Zhang Y., Wang T., Gao W., Yu S., Sun H., Pu J., Sun Y., Wang M., et al. IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection. Nat. Microbiol. 2021;6:932–945. doi: 10.1038/s41564-021-00907-x. PubMed DOI

Liao J.C., Lam R., Brazda V., Duan S., Ravichandran M., Ma J., Xiao T., Tempel W., Zuo X., Wang Y.-X., et al. Interferon-Inducible Protein 16: Insight into the Interaction with Tumor Suppressor p53. Structure. 2011;19:418–429. doi: 10.1016/j.str.2010.12.015. PubMed DOI PMC

Aglipay J.A., Lee S.W., Okada S., Fujiuchi N., Ohtsuka T., Kwak J.C., Wang Y., Johnstone R.W., Deng C., Qin J., et al. A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway. Oncogene. 2003;22:8931–8938. doi: 10.1038/sj.onc.1207057. PubMed DOI

Yu B., Zheng X., Sun Z., Cao P., Zhang J., Wang W. IFI16 Can Be Used as a Biomarker for Diagnosis of Renal Cell Carcinoma and Prediction of Patient Survival. Front. Genet. 2021;12:599952. doi: 10.3389/fgene.2021.599952. PubMed DOI PMC

Yu B., Zhang J., Sun Z., Cao P., Zheng X., Gao Z., Cao H., Zhang F., Wang W. Interferon-inducible protein 16 may be a biomarker and prognostic factor in renal cell carcinoma by bioinformatics analysis. Medicine. 2021;100:e24257. doi: 10.1097/MD.0000000000024257. PubMed DOI PMC

Cai H., Yan L., Liu N., Xu M., Cai H. IFI16 promotes cervical cancer progression by upregulating PD-L1 in immunomicroenvironment through STING-TBK1-NF-kB pathway. Biomed. Pharmacother. 2020;123:109790. doi: 10.1016/j.biopha.2019.109790. PubMed DOI

Lin W., Zhao Z., Ni Z., Zhao Y., Du W., Chen S. IFI16 restoration in hepatocellular carcinoma induces tumour inhibition via activation of p53 signals and inflammasome. Cell Prolif. 2017;50:e12392. doi: 10.1111/cpr.12392. PubMed DOI PMC

Mazibrada J., De Andrea M., Rittà M., Borgogna C., Dell’Eva R., Pfeffer U., Chiusa L., Gariglio M., Landolfo S. In vivo growth inhibition of head and neck squamous cell carcinoma by the Interferon-inducible gene IFI16. Cancer Lett. 2010;287:33–43. doi: 10.1016/j.canlet.2009.05.035. PubMed DOI

Xin H., Curry J., Johnstone R.W., Nickoloff B.J., Choubey D. Role of IFI 16, a member of the interferon-inducible p200-protein family, in prostate epithelial cellular senescence. Oncogene. 2003;22:4831–4840. doi: 10.1038/sj.onc.1206754. PubMed DOI

Fujiuchi N., Aglipay J.A., Ohtsuka T., Maehara N., Sahin F., Su G.H., Lee S.W., Ouchi T. Requirement of IFI16 for the Maximal Activation of p53 Induced by Ionizing Radiation. J. Biol. Chem. 2004;279:20339–20344. doi: 10.1074/jbc.M400344200. PubMed DOI

Chen T., Sun Y., Ji P., Kopetz S., Zhang W. Topoisomerase IIα in chromosome instability and personalized cancer therapy. Oncogene. 2014;34:4019–4031. doi: 10.1038/onc.2014.332. PubMed DOI PMC

Shinagawa H., Miki Y., Yoshida K. BRCA1-Mediated Ubiquitination Inhibits Topoisomerase IIα Activity in Response to Oxidative Stress. Antioxidants Redox Signal. 2008;10:939–950. doi: 10.1089/ars.2007.1851. PubMed DOI

Herrero-Ruiz A., Martínez-García P.M., Terrón-Bautista J., Millán-Zambrano G., Lieberman J.A., Jimeno-González S., Cortés-Ledesma F. Topoisomerase IIα represses transcription by enforcing promoter-proximal pausing. Cell Rep. 2021;35:108977. doi: 10.1016/j.celrep.2021.108977. PubMed DOI PMC

Meng H., Chen R., Li W., Xu L., Xu L. Correlations of TOP2A gene aberrations and expression of topoisomerase IIα protein and TOP2A mRNA expression in primary breast cancer: A retrospective study of 86 cases using fluorescence in situ hybridization and immunohistochemistry. Pathol. Int. 2012;62:391–399. doi: 10.1111/j.1440-1827.2012.02808.x. PubMed DOI

Depowski P.L., Rosenthal S.I., Brien T.P., Stylos S., Johnson R.L., Ross J.S. Topoisomerase IIα Expression in Breast Cancer: Correlation with Outcome Variables. Mod. Pathol. 2000;13:542–547. doi: 10.1038/modpathol.3880094. PubMed DOI

Washiro M., Ohtsuka M., Kimura F., Shimizu H., Yoshidome H., Sugimoto T., Seki N., Miyazaki M. Upregulation of topoisomerase IIα expression in advanced gallbladder carcinoma: A potential chemotherapeutic target. J. Cancer Res. Clin. Oncol. 2008;134:793–801. doi: 10.1007/s00432-007-0348-0. PubMed DOI

Lan J., Huang H.-Y., Lee S.-W., Chen T.-J., Tai H.-C., Hsu H.-P., Chang K.-Y., Li C.-F. TOP2A overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma. Tumor Biol. 2013;35:179–187. doi: 10.1007/s13277-013-1022-6. PubMed DOI

Zhang W.C.S. Sox2, a key factor in the regulation of pluripotency and neural differentiation. World J. Stem Cells. 2014;6:305–311. doi: 10.4252/wjsc.v6.i3.305. PubMed DOI PMC

Schaefer T., Lengerke C. SOX2 protein biochemistry in stemness, reprogramming, and cancer: The PI3K/AKT/SOX2 axis and beyond. Oncogene. 2020;39:278–292. doi: 10.1038/s41388-019-0997-x. PubMed DOI PMC

Ng S.-Y., Johnson R., Stanton L.W. Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors. EMBO J. 2012;31:522–533. doi: 10.1038/emboj.2011.459. PubMed DOI PMC

Guo X., Wang Z., Lu C., Hong W., Wang G., Xu Y., Liu Z., Kang J. LincRNA-1614 coordinates Sox2/PRC2-mediated repression of developmental genes in pluripotency maintenance. J. Mol. Cell Biol. 2018;10:118–129. doi: 10.1093/jmcb/mjx041. PubMed DOI PMC

Holmes Z.E., Hamilton D.J., Hwang T., Parsonnet N.V., Rinn J.L., Wuttke D.S., Batey R.T. The Sox2 transcription factor binds RNA. Nat. Commun. 2020;11:1805. doi: 10.1038/s41467-020-15571-8. PubMed DOI PMC

Wuebben E.L., Rizzino A. The dark side of SOX2: Cancer—A comprehensive overview. Oncotarget. 2017;8:44917–44943. doi: 10.18632/oncotarget.16570. PubMed DOI PMC

Grimm D., Bauer J., Wise P., Krüger M., Simonsen U., Wehland M., Infanger M., Corydon T.J. The role of SOX family members in solid tumours and metastasis. Semin. Cancer Biol. 2019;67:122–153. doi: 10.1016/j.semcancer.2019.03.004. PubMed DOI

Jin S., Zhan J., Zhou Y. Argonaute proteins: Structures and their endonuclease activity. Mol. Biol. Rep. 2021;48:4837–4849. doi: 10.1007/s11033-021-06476-w. PubMed DOI

Hutvagner G., Simard M.J. Argonaute proteins: Key players in RNA silencing. Nat. Rev. Mol. Cell Biol. 2008;9:22–32. doi: 10.1038/nrm2321. PubMed DOI

Yang Y., Mei Q. Accumulation of AGO2 Facilitates Tumorigenesis of Human Hepatocellular Carcinoma. BioMed Res. Int. 2020;2020:1631843. doi: 10.1155/2020/1631843. PubMed DOI PMC

Vaksman O., Hetland T.E., Trope’ C.G., Reich R., Davidson B. Argonaute, Dicer, and Drosha are up-regulated along tumor progression in serous ovarian carcinoma. Hum. Pathol. 2012;43:2062–2069. doi: 10.1016/j.humpath.2012.02.016. PubMed DOI

Zhang J., Fan X.-S., Wang C.-X., Liu B., Li Q., Zhou X.-J. Up-regulation of Ago2 expression in gastric carcinoma. Med. Oncol. 2013;30:628. doi: 10.1007/s12032-013-0628-2. PubMed DOI

Niu F., Dzikiewicz-Krawczyk A., Koerts J., De Jong D., Wijenberg L., Hernandez M.F., Slezak-Prochazka I., Winkle M., Kooistra W., Van Der Sluis T., et al. MiR-378a-3p Is Critical for Burkitt Lymphoma Cell Growth. Cancers. 2020;12:3546. doi: 10.3390/cancers12123546. PubMed DOI PMC

Liu X., Meng X., Peng X., Yao Q., Zhu F., Ding Z., Sun H., Liu X., Li D., Lu Y., et al. Impaired AGO2/miR-185-3p/NRP1 axis promotes colorectal cancer metastasis. Cell Death Dis. 2021;12:390. doi: 10.1038/s41419-021-03672-1. PubMed DOI PMC

Shankar S., Tien J.C.-Y., Siebenaler R.F., Chugh S., Dommeti V.L., Zelenka-Wang S., Wang X.-M., Apel I.J., Waninger J., Eyunni S., et al. An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development. Nat. Commun. 2020;11:28. doi: 10.1038/s41467-020-16309-2. PubMed DOI PMC

Tien J.C.-Y., Chugh S., Goodrum A.E., Cheng Y., Mannan R., Zhang Y., Wang L., Dommeti V.L., Wang X., Xu A., et al. AGO2 promotes tumor progression in KRAS-driven mouse models of non–small cell lung cancer. Proc. Natl. Acad. Sci. USA. 2021;118:e2026104118. doi: 10.1073/pnas.2026104118. PubMed DOI PMC

Unal O., Akkoc Y., Kocak M., Nalbat E., Dogan-Ekici A.I., Acar H.Y., Gozuacik D. Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles. J. Nanobiotechnol. 2020;18:65. doi: 10.1186/s12951-020-00615-4. PubMed DOI PMC

Li K., Wu J.-L., Qin B., Fan Z., Tang Q., Lu W., Zhang H., Xing F., Meng M., Zou S., et al. ILF3 is a substrate of SPOP for regulating serine biosynthesis in colorectal cancer. Cell Res. 2020;30:163–178. doi: 10.1038/s41422-019-0257-1. PubMed DOI PMC

Li Y., Zhao Y., Liu Y., Fan L., Jia N., Zhao Q. ILF3 promotes gastric cancer proliferation and may be used as a prognostic marker. Mol. Med. Rep. 2019;20:125–134. doi: 10.3892/mmr.2019.10229. PubMed DOI PMC

Xu Z., Huang H., Li X., Ji C., Liu Y., Liu X., Zhu J., Wang Z., Zhang H., Shi J. High expression of interleukin-enhancer binding factor 3 predicts poor prognosis in patients with lung adenocarcinoma. Oncol. Lett. 2020;19:2141–2152. doi: 10.3892/ol.2020.11330. PubMed DOI PMC

Bremer H.D., Landegren N., Sjöberg R., Hallgren Å., Renneker S., Lattwein E., Leonard D., Eloranta M.-L., Rönnblom L., Nordmark G., et al. ILF2 and ILF3 are autoantigens in canine systemic autoimmune disease. Sci. Rep. 2018;8:4852. doi: 10.1038/s41598-018-23034-w. PubMed DOI PMC

Izumi T., Fujii R., Izumi T., Nakazawa M., Yagishita N., Tsuchimochi K., Yamano Y., Sato T., Fujita H., Aratani S., et al. Activation of synoviolin promoter in rheumatoid synovial cells by a novel transcription complex of interleukin enhancer binding factor 3 and GA binding protein α. Arthritis Care Res. 2008;60:63–72. doi: 10.1002/art.24178. PubMed DOI

Park C.Y., Zhou J., Wong A.K., Chen K.M., Theesfeld C.L., Darnell R., Troyanskaya O.G. Genome-wide landscape of RNA-binding protein target site dysregulation reveals a major impact on psychiatric disorder risk. Nat. Genet. 2021;53:166–173. doi: 10.1038/s41588-020-00761-3. PubMed DOI PMC

Corthésy B., Kao P. Purification by DNA affinity chromatography of two polypeptides that contact the NF-AT DNA binding site in the interleukin 2 promoter. J. Biol. Chem. 1994;269:20682–20690. doi: 10.1016/S0021-9258(17)32047-1. PubMed DOI

Kao P., Chen L., Brock G., Ng J., Kenny J., Smith A., Corthésy B. Cloning and expression of cyclosporin A- and FK506-sensitive nuclear factor of activated T-cells: NF45 and NF90. J. Biol. Chem. 1994;269:20691–20699. doi: 10.1016/S0021-9258(17)32048-3. PubMed DOI

Thandapani P., O’Connor T.R., Bailey T.L., Richard S. Defining the RGG/RG Motif. Mol. Cell. 2013;50:613–623. doi: 10.1016/j.molcel.2013.05.021. PubMed DOI

Shiina N., Nakayama K. RNA Granule Assembly and Disassembly Modulated by Nuclear Factor Associated with Double-stranded RNA 2 and Nuclear Factor 45. J. Biol. Chem. 2014;289:21163–21180. doi: 10.1074/jbc.M114.556365. PubMed DOI PMC

Reichman T.W., Parrott A.M., Fierro-Monti I., Caron D.J., Kao P.N., Lee C.-G., Li H., Mathews M.B. Selective Regulation of Gene Expression by Nuclear Factor 110, a Member of the NF90 Family of Double-stranded RNA-binding Proteins. J. Mol. Biol. 2003;332:85–98. doi: 10.1016/S0022-2836(03)00885-4. PubMed DOI

Wu T.H., Shi L., Adrian J., Shi M., Nair R.V., Snyder M.P., Kao P.N. NF90/ILF3 is a transcription factor that promotes proliferation over differentiation by hierarchical regulation in K562 erythroleukemia cells. PLoS ONE. 2018;13:e0193126. doi: 10.1371/journal.pone.0193126. PubMed DOI PMC

Freund E.C., Sapiro A.L., Li Q., Linder S., Moresco J.J., Yates J.R., Li J.B. Unbiased Identification of trans Regulators of ADAR and A-to-I RNA Editing. Cell Rep. 2020;31:107656. doi: 10.1016/j.celrep.2020.107656. PubMed DOI PMC

Chan T.W., Fu T., Bahn J.H., Jun H.-I., Lee J.-H., Quinones-Valdez G., Cheng C., Xiao X. RNA editing in cancer impacts mRNA abundance in immune response pathways. Genome Biol. 2020;21:268. doi: 10.1186/s13059-020-02171-4. PubMed DOI PMC

Li D., She J., Hu X., Zhang M., Sun R., Qin S. The ELF3-regulated lncRNA UBE2CP3 is over-stabilized by RNA–RNA interactions and drives gastric cancer metastasis via miR-138-5p/ITGA2 axis. Oncogene. 2021;40:5403–5415. doi: 10.1038/s41388-021-01948-6. PubMed DOI PMC

Nussbacher J.K., Yeo G.W. Systematic Discovery of RNA Binding Proteins that Regulate MicroRNA Levels. Mol. Cell. 2018;69:1005–1016.e7. doi: 10.1016/j.molcel.2018.02.012. PubMed DOI PMC

Li Y., Wang M., Yang M., Xiao Y., Jian Y., Shi D., Chen X., Ouyang Y., Kong L., Huang X., et al. Nicotine-Induced ILF2 Facilitates Nuclear mRNA Export of Pluripotency Factors to Promote Stemness and Chemoresistance in Human Esophageal Cancer. Cancer Res. 2021;81:3525–3538. doi: 10.1158/0008-5472.CAN-20-4160. PubMed DOI

Garcìa J.B., Eufemiese R., Storti P., Sammarelli G., Craviotto L., Todaro G., Toscani D., Marchica V., Giuliani N. Role of 1q21 in Multiple Myeloma: From Pathogenesis to Possible Therapeutic Targets. Cells. 2021;10:1360. doi: 10.3390/cells10061360. PubMed DOI PMC

Marchesini M., Ogoti Y., Fiorini E., Samur A.A., Nezi L., D’Anca M., Storti P., Samur M.K., Gañán-Gómez I., Fulciniti M.T., et al. ILF2 Is a Regulator of RNA Splicing and DNA Damage Response in 1q21-Amplified Multiple Myeloma. Cancer Cell. 2017;32:88–100.e6. doi: 10.1016/j.ccell.2017.05.011. PubMed DOI PMC

Zhao M., Liu Y., Chang J., Qi J., Liu R., Hou Y., Wang Y., Zhang X., Qiao L., Ren L. ILF2 cooperates with E2F1 to maintain mitochondrial homeostasis and promote small cell lung cancer progression. Cancer Biol. Med. 2019;16:771–783. doi: 10.20892/j.issn.2095-3941.2019.0050. PubMed DOI PMC

Li N., Liu T., Li H., Zhang L., Chu L., Meng Q., Qiao Q., Han W., Zhang J., Guo M., et al. ILF2 promotes anchorage independence through direct regulation of PTEN. Oncol. Lett. 2019;18:1689–1696. doi: 10.3892/ol.2019.10510. PubMed DOI PMC

Lei X., Shen X., Xu X., Bernstein H. Human Cdc5, a regulator of mitotic entry, can act as a site-specific DNA binding protein. Pt 24J. Cell Sci. 2000;113:4523–4531. doi: 10.1242/jcs.113.24.4523. PubMed DOI

Liu L., Gräub R., Hlaing M., Epting C.L., Turck C.W., Xu X.-Q., Zhang L., Bernstein H.S. Distinct Domains of Human CDC5 Direct Its Nuclear Import and Association with the Spliceosome. Cell Biophys. 2003;39:119–132. doi: 10.1385/CBB:39:2:119. PubMed DOI

Neubauer G., King A., Rappsilber J., Calvio C., Watson M., Ajuh P., Sleeman J., Lamond A., Mann M. Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex. Nat. Genet. 1998;20:46–50. doi: 10.1038/1700. PubMed DOI

Munschauer M., Nguyen C.T., Sirokman K., Hartigan C.R., Hogstrom L., Engreitz J.M., Ulirsch J.C., Fulco C.P., Subramanian V., Chen J., et al. The NORAD lncRNA assembles a topoisomerase complex critical for genome stability. Nature. 2018;561:132–136. doi: 10.1038/s41586-018-0453-z. PubMed DOI

Ajuh P., Kuster B., Panov K., Zomerdijk J., Mann M., Lamond A. Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry. EMBO J. 2000;19:6569–6581. doi: 10.1093/emboj/19.23.6569. PubMed DOI PMC

Ohi R., Mccollum D., Hirani B., Haese G.D., Zhang X., Burke J., Turner K., Gould K. The Schizosaccharomyces pombe cdc5+ gene encodes an essential protein with homology to c-Myb. EMBO J. 1994;13:471–483. doi: 10.1002/j.1460-2075.1994.tb06282.x. PubMed DOI PMC

Zhang H.-Y., Li J., Ouyang Y.-C., Meng T.-G., Zhang C.-H., Yue W., Sun Q.-Y., Qian W.-P. Cell Division Cycle 5-Like Regulates Metaphase-to-Anaphase Transition in Meiotic Oocyte. Front. Cell Dev. Biol. 2021;9:671685. doi: 10.3389/fcell.2021.671685. PubMed DOI PMC

Gräub R., Lancero H., Pedersen A., Chu M., Padmanabhan K., Xu X.-Q., Spitz P., Chalkley R., Burlingame A.L., Stokoe D., et al. Cell cycle-dependent phosphorylation of human CDC5 regulates RNA processing. Cell Cycle. 2008;7:1795–1803. doi: 10.4161/cc.7.12.6017. PubMed DOI PMC

de Moura T.R., Mozaffari-Jovin S., Szabó C.Z.K., Schmitzová J., Dybkov O., Cretu C., Kachala M., Svergun D., Urlaub H., Lührmann R., et al. Prp19/Pso4 Is an Autoinhibited Ubiquitin Ligase Activated by Stepwise Assembly of Three Splicing Factors. Mol. Cell. 2018;69:979–992.e6. doi: 10.1016/j.molcel.2018.02.022. PubMed DOI

Lu X., Legerski R.J. The Prp19/Pso4 core complex undergoes ubiquitylation and structural alterations in response to DNA damage. Biochem. Biophys. Res. Commun. 2007;354:968–974. doi: 10.1016/j.bbrc.2007.01.097. PubMed DOI PMC

Zhang N., Kaur R., Akhter S., Legerski R.J. Cdc5L interacts with ATR and is required for the S-phase cell-cycle checkpoint. EMBO Rep. 2009;10:1029–1035. doi: 10.1038/embor.2009.122. PubMed DOI PMC

Chen W., Zhang L., Wang Y., Sun J., Wang D., Fan S., Ban N., Zhu J., Ji B., Wang Y. Expression of CDC5L is associated with tumor progression in gliomas. Tumor Biol. 2015;37:4093–4103. doi: 10.1007/s13277-015-4088-5. PubMed DOI

Huang R., Xue R., Qu D., Yin J., Shen X.-Z. Prp19 Arrests Cell Cycle via Cdc5L in Hepatocellular Carcinoma Cells. Int. J. Mol. Sci. 2017;18:778. doi: 10.3390/ijms18040778. PubMed DOI PMC

Qiu H., Zhang X., Ni W., Shi W., Fan H., Xu J., Chen Y., Ni R., Tao T. Expression and Clinical Role of Cdc5L as a Novel Cell Cycle Protein in Hepatocellular Carcinoma. Am. J. Dig. Dis. 2015;61:795–805. doi: 10.1007/s10620-015-3937-9. PubMed DOI

Zhang Z., Mao W., Wang L., Liu M., Zhang W., Wu Y., Zhang J., Mao S., Geng J., Yao X. Depletion of CDC5L inhibits bladder cancer tumorigenesis. J. Cancer. 2020;11:353–363. doi: 10.7150/jca.32850. PubMed DOI PMC

Li J., Zhang N., Zhang R., Sun L., Yu W., Guo W., Gao Y., Li M., Liu W., Liang P., et al. CDC5L Promotes hTERT Expression and Colorectal Tumor Growth. Cell. Physiol. Biochem. 2017;41:2475–2488. doi: 10.1159/000475916. PubMed DOI

Gu Z., Zhang H., Li Y., Shen S., Yin X., Zhang W., Cheng R., Zhang Y., Zhang X., Chen H., et al. CDC5L drives FAH expression to promote metabolic reprogramming in melanoma. Oncotarget. 2017;8:114328–114343. doi: 10.18632/oncotarget.23107. PubMed DOI PMC

Zhang C., Li Y., Zhao W., Liu G., Yang Q. Circ-PGAM1 promotes malignant progression of epithelial ovarian cancer through regulation of the miR-542-3p/CDC5L/PEAK1 pathway. Cancer Med. 2020;9:3500–3521. doi: 10.1002/cam4.2929. PubMed DOI PMC

Li X., Wang X., Song W., Xu H., Huang R., Wang Y., Zhao W., Xiao Z., Yang X. Oncogenic Properties of NEAT1 in Prostate Cancer Cells Depend on the CDC5L–AGRN Transcriptional Regulation Circuit. Cancer Res. 2018;78:4138–4149. doi: 10.1158/0008-5472.CAN-18-0688. PubMed DOI

Zullo A.J., Michaud M., Zhang W., Grusby M.J. Identification of the Small Protein Rich in Arginine and Glycine (SRAG): A Newly Identified Nucleolar Protein That Can Regulate Cell Proliferation. J. Biol. Chem. 2009;284:12504–12511. doi: 10.1074/jbc.M809436200. PubMed DOI PMC

van Dijk T.B., Gillemans N., Stein C., Fanis P., Demmers J., van de Corput M., Essers J., Grosveld F., Bauer U.-M., Philipsen S. Friend of Prmt1, a Novel Chromatin Target of Protein Arginine Methyltransferases. Mol. Cell. Biol. 2010;30:260–272. doi: 10.1128/MCB.00645-09. PubMed DOI PMC

Chang C.-T., Hautbergue G.M., Walsh M.J., Viphakone N., Van Dijk T.B., Philipsen S., Wilson S.A. Chtop is a component of the dynamic TREX mRNA export complex. EMBO J. 2013;32:473–486. doi: 10.1038/emboj.2012.342. PubMed DOI PMC

Viphakone N., Sudbery I., Griffith L., Heath C.G., Sims D., Wilson S.A. Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome. Mol. Cell. 2019;75:310–323.e8. doi: 10.1016/j.molcel.2019.04.034. PubMed DOI PMC

Izumikawa K., Yoshikawa H., Ishikawa H., Nobe Y., Yamauchi Y., Philipsen S., Simpson R.J., Isobe T., Takahashi N. Chtop (Chromatin target of Prmt1) auto-regulates its expression level via intron retention and nonsense-mediated decay of its own mRNA. Nucleic Acids Res. 2016;44:9847–9859. doi: 10.1093/nar/gkw831. PubMed DOI PMC

Takai H., Masuda K., Sato T., Sakaguchi Y., Suzuki T., Suzuki T., Koyama-Nasu R., Nasu-Nishimura Y., Katou Y., Ogawa H., et al. 5-Hydroxymethylcytosine Plays a Critical Role in Glioblastomagenesis by Recruiting the CHTOP-Methylosome Complex. Cell Rep. 2014;9:48–60. doi: 10.1016/j.celrep.2014.08.071. PubMed DOI

Feng X., Bai X., Ni J., Wasinger V.C., Beretov J., Zhu Y., Graham P., Li Y. CHTOP in Chemoresistant Epithelial Ovarian Cancer: A Novel and Potential Therapeutic Target. Front. Oncol. 2019;9:557. doi: 10.3389/fonc.2019.00557. PubMed DOI PMC

Feng X., Li L., Wang L., Luo S., Bai X. Chromatin target of protein arginine methyltransferase regulates invasion, chemoresistance, and stemness in epithelial ovarian cancer. Biosci. Rep. 2019;39:BSR20190016. doi: 10.1042/BSR20190016. PubMed DOI PMC

Li R., Liu Y., Hou Y., Gan J., Wu P., Li C. 3D genome and its disorganization in diseases. Cell Biol. Toxicol. 2018;34:351–365. doi: 10.1007/s10565-018-9430-4. PubMed DOI

Rowley M.J., Corces V.G. The three-dimensional genome: Principles and roles of long-distance interactions. Curr. Opin. Cell Biol. 2016;40:8–14. doi: 10.1016/j.ceb.2016.01.009. PubMed DOI PMC

Fackelmayer F.O., Dahm K., Renz A., Ramsperger U., Richter A. Nucleic-acid-binding properties of hnRNP-U/SAF-A, a nuclear-matrix protein which binds DNA and RNA in vivo and in vitro. JBIC J. Biol. Inorg. Chem. 1994;221:749–757. doi: 10.1111/j.1432-1033.1994.tb18788.x. PubMed DOI

Hasegawa Y., Brockdorff N., Kawano S., Tsutui K., Tsutui K., Nakagawa S. The Matrix Protein hnRNP U Is Required for Chromosomal Localization of Xist RNA. Dev. Cell. 2010;19:469–476. doi: 10.1016/j.devcel.2010.08.006. PubMed DOI

Davis M., Hatzubai A., Andersen J.S., Ben-Shushan E., Fisher G.Z., Yaron A., Bauskin A., Mercurio F., Mann M., Ben-Neriah Y. Pseudosubstrate regulation of the SCFβ-TrCP ubiquitin ligase by hnRNP-U. Genes Dev. 2002;16:439–451. doi: 10.1101/gad.218702. PubMed DOI PMC

Martens J.H.A., Verlaan M., Kalkhoven E., Dorsman J.C., Zantema A. Scaffold/Matrix Attachment Region Elements Interact with a p300—Scaffold Attachment Factor A Complex and Are Bound by Acetylated Nucleosomes. Mol. Cell. Biol. 2002;22:2598–2606. doi: 10.1128/MCB.22.8.2598-2606.2002. PubMed DOI PMC

Kukalev A., Nord Y., Palmberg C., Bergman T., Percipalle P. Actin and hnRNP U cooperate for productive transcription by RNA polymerase II. Nat. Struct. Mol. Biol. 2005;12:238–244. doi: 10.1038/nsmb904. PubMed DOI

Spraggon L., Dudnakova T., Slight J., Lustig-Yariv O., Cotterell J., Hastie N., Miles C. hnRNP-U directly interacts with WT1 and modulates WT1 transcriptional activation. Oncogene. 2006;26:1484–1491. doi: 10.1038/sj.onc.1209922. PubMed DOI

Helbig R., Fackelmayer F.O. Scaffold attachment factor A (SAF-A) is concentrated in inactive X chromosome territories through its RGG domain. Chromosoma. 2003;112:173–182. doi: 10.1007/s00412-003-0258-0. PubMed DOI

McHugh C.A., Chen C.-K., Chow A., Surka C.F., Tran C., McDonel P., Pandya-Jones A., Blanco M., Burghard C., Moradian A., et al. The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. Nature. 2015;521:232–236. doi: 10.1038/nature14443. PubMed DOI PMC

Xiao R., Tang P., Yang B., Huang J., Zhou Y., Shao C., Li H., Sun H., Zhang Y., Fu X.-D. Nuclear Matrix Factor hnRNP U/SAF-A Exerts a Global Control of Alternative Splicing by Regulating U2 snRNP Maturation. Mol. Cell. 2012;45:656–668. doi: 10.1016/j.molcel.2012.01.009. PubMed DOI PMC

Britton S., Froment C., Frit P., Monsarrat B., Salles B., Calsou P. Cell nonhomologous end joining capacity controls SAF-A phosphorylation by DNA-PK in response to DNA double-strand breaks inducers. Cell Cycle. 2009;8:3717–3722. doi: 10.4161/cc.8.22.10025. PubMed DOI

Izumi H., Funa K. Telomere Function and the G-Quadruplex Formation are Regulated by hnRNP U. Cells. 2019;8:390. doi: 10.3390/cells8050390. PubMed DOI PMC

Xing S., Li Z., Ma W., He X., Shen S., Wei H., Li S.-T., Shu Y., Sun L., Zhong X., et al. DIS3L2 Promotes Progression of Hepatocellular Carcinoma via hnRNP U-Mediated Alternative Splicing. Cancer Res. 2019;79:4923–4936. doi: 10.1158/0008-5472.CAN-19-0376. PubMed DOI

Nishikawa T., Kuwano Y., Takahara Y., Nishida K., Rokutan K. HnRNPA1 interacts with G-quadruplex in the TRA2B promoter and stimulates its transcription in human colon cancer cells. Sci. Rep. 2019;9:10276. doi: 10.1038/s41598-019-46659-x. PubMed DOI PMC

Song H., Li D., Wang X., Fang E., Yang F., Hu A., Wang J., Guo Y., Liu Y., Li H., et al. HNF4A-AS1/hnRNPU/CTCF axis as a therapeutic target for aerobic glycolysis and neuroblastoma progression. J. Hematol. Oncol. 2020;13:24. doi: 10.1186/s13045-020-00857-7. PubMed DOI PMC

Sutaria D.S., Jiang J., Azevedo-Pouly A.C.P., Lee E.J., Lerner M.R., Brackett D.J., Vandesompele J., Mestdagh P., Schmittgen T.D. Expression Profiling Identifies the Noncoding Processed Transcript of HNRNPU with Proliferative Properties in Pancreatic Ductal Adenocarcinoma. Non-Coding RNA. 2017;3:24. doi: 10.3390/ncrna3030024. PubMed DOI PMC

Piñol-Roma S., Swanson M., Gall J.G., Dreyfuss G. A novel heterogeneous nuclear RNP protein with a unique distribution on nascent transcripts. J. Cell Biol. 1989;109:2575–2587. doi: 10.1083/jcb.109.6.2575. PubMed DOI PMC

Shankarling G., Lynch K.W. Minimal functional domains of paralogues hnRNP L and hnRNP LL exhibit mechanistic differences in exonic splicing repression. Biochem. J. 2013;453:271–279. doi: 10.1042/BJ20130432. PubMed DOI PMC

Gu J., Chen Z., Chen X., Wang Z. Heterogeneous nuclear ribonucleoprotein (hnRNPL) in cancer. Clin. Chim. Acta. 2020;507:286–294. doi: 10.1016/j.cca.2020.04.040. PubMed DOI

Fei T., Chen Y., Xiao T., Li W., Cato L., Zhang P., Cotter M.B., Bowden M., Lis R.T., Zhao S.G., et al. Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proc. Natl. Acad. Sci. USA. 2017;114:E5207–E5215. doi: 10.1073/pnas.1617467114. PubMed DOI PMC

Chen C., He W., Huang J., Wang B., Li H., Cai Q., Su F., Bi J., Liu H., Zhang B., et al. LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment. Nat. Commun. 2018;9:3826. doi: 10.1038/s41467-018-06152-x. PubMed DOI PMC

Klingenberg M., Groß M., Goyal A., Polycarpou-Schwarz M., Miersch T., Ernst A., Leupold J., Patil N., Warnken U., Allgayer H., et al. The Long Noncoding RNA Cancer Susceptibility 9 and RNA Binding Protein Heterogeneous Nuclear Ribonucleoprotein L Form a Complex and Coregulate Genes Linked to AKT Signaling. Hepatology. 2018;68:1817–1832. doi: 10.1002/hep.30102. PubMed DOI

He X., Chai P., Li F., Zhang L., Zhou C., Yuan X., Li Y., Yang J., Luo Y., Ge S., et al. A novel LncRNA transcript, RBAT1, accelerates tumorigenesis through interacting with HNRNPL and cis-activating E2F3. Mol. Cancer. 2020;19:115. doi: 10.1186/s12943-020-01232-3. PubMed DOI PMC

Li Y., Chen B., Zhao J., Li Q., Chen S., Guo T., Li Y., Lai H., Chen Z., Meng Z., et al. HNRNPL Circularizes ARHGAP35 to Produce an Oncogenic Protein. Adv. Sci. 2021;8:2001701. doi: 10.1002/advs.202001701. PubMed DOI PMC

Goodwin J.F., Knudsen K.E. Beyond DNA Repair: DNA-PK Function in Cancer. Cancer Discov. 2014;4:1126–1139. doi: 10.1158/2159-8290.CD-14-0358. PubMed DOI PMC

Mohiuddin I.S., Kang M.H. DNA-PK as an Emerging Therapeutic Target in Cancer. Front. Oncol. 2019;9:635. doi: 10.3389/fonc.2019.00635. PubMed DOI PMC

Jackson S.P., MacDonald J.J., Lees-Miller S., Tjian R. GC box binding induces phosphorylation of Sp1 by a DNA-dependent protein kinase. Cell. 1990;63:155–165. doi: 10.1016/0092-8674(90)90296-Q. PubMed DOI

Kim Y.K., Maquat L.E. UPFront and center in RNA decay: UPF1 in nonsense-mediated mRNA decay and beyond. RNA. 2019;25:407–422. doi: 10.1261/rna.070136.118. PubMed DOI PMC

Boehm V., Kueckelmann S., Gerbracht J.V., Kallabis S., Britto-Borges T., Altmüller J., Krüger M., Dieterich C., Gehring N.H. SMG5-SMG7 authorize nonsense-mediated mRNA decay by enabling SMG6 endonucleolytic activity. Nat. Commun. 2021;12:3965. doi: 10.1038/s41467-021-24046-3. PubMed DOI PMC

Nogueira G., Fernandes R., García-Moreno J.F., Romão L. Nonsense-mediated RNA decay and its bipolar function in cancer. Mol. Cancer. 2021;20:72. doi: 10.1186/s12943-021-01364-0. PubMed DOI PMC

Bokhari A., Jonchere V., Lagrange A., Bertrand R., Svrcek M., Marisa L., Buhard O., Greene M., Demidova A., Jia J., et al. Targeting nonsense-mediated mRNA decay in colorectal cancers with microsatellite instability. Oncogenesis. 2018;7:70. doi: 10.1038/s41389-018-0079-x. PubMed DOI PMC

Kashima I., Yamashita A., Izumi N., Kataoka N., Morishita R., Hoshino S., Ohno M., Dreyfuss G., Ohno S. Binding of a novel SMG-1–Upf1–eRF1–eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay. Genes Dev. 2006;20:355–367. doi: 10.1101/gad.1389006. PubMed DOI PMC

Gewandter J.S., Bambara R.A., O’Reilly M.A. The RNA surveillance protein SMG1 activates p53 in response to DNA double-strand breaks but not exogenously oxidized mRNA. Cell Cycle. 2011;10:2561–2567. doi: 10.4161/cc.10.15.16347. PubMed DOI PMC

Chen J., Crutchley J., Zhang D., Owzar K., Kastan M.B. Identification of a DNA Damage–Induced Alternative Splicing Pathway That Regulates p53 and Cellular Senescence Markers. Cancer Discov. 2017;7:766–781. doi: 10.1158/2159-8290.CD-16-0908. PubMed DOI PMC

Azzalin C.M., Reichenbach P., Khoriauli L., Giulotto E., Lingner J. Telomeric Repeat–Containing RNA and RNA Surveillance Factors at Mammalian Chromosome Ends. Science. 2007;318:798–801. doi: 10.1126/science.1147182. PubMed DOI

McIlwain D.R., Pan Q., Reilly P.T., Elia A.J., McCracken S., Wakeham A.C., Itie-Youten A., Blencowe B.J., Mak T.W. Smg1 is required for embryogenesis and regulates diverse genes via alternative splicing coupled to nonsense-mediated mRNA decay. Proc. Natl. Acad. Sci. USA. 2010;107:12186–12191. doi: 10.1073/pnas.1007336107. PubMed DOI PMC

Roberts T.L., Ho U., Luff J., Lee C.S., Apte S.H., MacDonald K.P.A., Raggat L.J., Pettit A.R., Morrow C.A., Waters M.J., et al. Smg1 haploinsufficiency predisposes to tumor formation and inflammation. Proc. Natl. Acad. Sci. USA. 2012;110:E285–E294. doi: 10.1073/pnas.1215696110. PubMed DOI PMC

Du Y., Lu F., Li P., Ye J., Ji M., Ma D., Ji C. SMG1 Acts as a Novel Potential Tumor Suppressor with Epigenetic Inactivation in Acute Myeloid Leukemia. Int. J. Mol. Sci. 2014;15:17065–17076. doi: 10.3390/ijms150917065. PubMed DOI PMC

Wang G., Jiang B., Jia C., Chai B., Liang A. MicroRNA 125 represses nonsense-mediated mRNA decay by regulating SMG1 expression. Biochem. Biophys. Res. Commun. 2013;435:16–20. doi: 10.1016/j.bbrc.2013.03.129. PubMed DOI

Zeng S., Liu S., Feng J., Gao J., Xue F. MicroRNA-32 promotes ovarian cancer cell proliferation and motility by targeting SMG1. Oncol. Lett. 2020;20:733–741. doi: 10.3892/ol.2020.11624. PubMed DOI PMC

Mai S., Xiao R., Shi L., Zhou X., Yang T., Zhang M., Weng N., Zhao X., Wang R., Liu J., et al. MicroRNA-18a promotes cancer progression through SMG1 suppression and mTOR pathway activation in nasopharyngeal carcinoma. Cell Death Dis. 2019;10:819. doi: 10.1038/s41419-019-2060-9. PubMed DOI PMC

Zhang X., Peng Y., Huang Y., Yang M., Yan R., Zhao Y., Cheng Y., Liu X., Deng S., Feng X., et al. SMG-1 inhibition by miR-192/-215 causes epithelial-mesenchymal transition in gastric carcinogenesis via activation of Wnt signaling. Cancer Med. 2017;7:146–156. doi: 10.1002/cam4.1237. PubMed DOI PMC

Han L.-L., Nan H.-C., Tian T., Guo H., Hu T.-H., Wang W.-J., Ma J.-Q., Jiang L.-L., Guo Q.-Q., Yang C.-C., et al. Expression and significance of the novel tumor-suppressor gene SMG-1 in hepatocellular carcinoma. Oncol. Rep. 2014;31:2569–2578. doi: 10.3892/or.2014.3125. PubMed DOI

Schmidt J.C., Dalby A.B., Cech T.R. Identification of human TERT elements necessary for telomerase recruitment to telomeres. eLife. 2014;3:e03563. doi: 10.7554/eLife.03563. PubMed DOI PMC

Shay J.W., Bacchetti S. A survey of telomerase activity in human cancer. Eur. J. Cancer. 1997;33:787–791. doi: 10.1016/S0959-8049(97)00062-2. PubMed DOI

Barthel F.P., Wei W., Tang M., Martinez-Ledesma E., Hu X., Amin S.B., Akdemir K.C., Seth S., Song X., Wang Q., et al. Systematic analysis of telomere length and somatic alterations in 31 cancer types. Nat. Genet. 2017;49:349–357. doi: 10.1038/ng.3781. PubMed DOI PMC

Zhang Y., Chen Y., Yang C., Seger N., Hesla A.C., Tsagkozis P., Larsson O., Lin Y., Haglund F. TERT promoter mutation is an objective clinical marker for disease progression in chondrosarcoma. Mod. Pathol. 2021;34:2020–2027. doi: 10.1038/s41379-021-00848-0. PubMed DOI PMC

Lee Y., Koh J., Kim S.-I., Won J.K., Park C.-K., Choi S.H., Park S.-H. The frequency and prognostic effect of TERT promoter mutation in diffuse gliomas. Acta Neuropathol. Commun. 2017;5:62. doi: 10.1186/s40478-017-0465-1. PubMed DOI PMC

Geng P., Zhao X., Ou J., Li J., Sa R., Liang H. TERT Genetic Mutations as Prognostic Marker in Glioma. Mol. Neurobiol. 2016;54:3665–3669. doi: 10.1007/s12035-016-9930-2. PubMed DOI

Jang J.-W., Kim J.-S., Kim H.-S., Tak K.-Y., Lee S.-K., Nam H.-C., Sung P.-S., Kim C.-M., Park J.-Y., Bae S.-H., et al. Significance of TERT Genetic Alterations and Telomere Length in Hepatocellular Carcinoma. Cancers. 2021;13:2160. doi: 10.3390/cancers13092160. PubMed DOI PMC

Saraswati A.P., Relitti N., Brindisi M., Gemma S., Zisterer D., Butini S., Campiani G. Raising the bar in anticancer therapy: Recent advances in, and perspectives on, telomerase inhibitors. Drug Discov. Today. 2019;24:1370–1388. doi: 10.1016/j.drudis.2019.05.015. PubMed DOI

Jonas S., Weichenrieder O., Izaurralde E. An unusual arrangement of two 14-3-3-like domains in the SMG5–SMG7 heterodimer is required for efficient nonsense-mediated mRNA decay. Genes Dev. 2013;27:211–225. doi: 10.1101/gad.206672.112. PubMed DOI PMC

Glavan F., Behm-Ansmant I., Izaurralde E., Conti E. Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex. EMBO J. 2006;25:5117–5125. doi: 10.1038/sj.emboj.7601377. PubMed DOI PMC

Ohnishi T., Yamashita A., Kashima I., Schell T., Anders K.R., Grimson A., Hachiya T., Hentze M.W., Anderson P., Ohno S. Phosphorylation of hUPF1 Induces Formation of mRNA Surveillance Complexes Containing hSMG-5 and hSMG-7. Mol. Cell. 2003;12:1187–1200. doi: 10.1016/S1097-2765(03)00443-X. PubMed DOI

Man Z., Chen Y., Gao L., Xei G., Li Q., Lu Q., Yan J. A Prognostic Model Based on RNA Binding Protein Predicts Clinical Outcomes in Hepatocellular Carcinoma Patients. Front. Oncol. 2021;10:613102. doi: 10.3389/fonc.2020.613102. PubMed DOI PMC

Li Q., Karim R.M., Cheng M., Das M., Chen L., Zhang C., Lawrence H.R., Daughdrill G.W., Schonbrunn E., Ji H., et al. Inhibition of p53 DNA binding by a small molecule protects mice from radiation toxicity. Oncogene. 2020;39:5187–5200. doi: 10.1038/s41388-020-1344-y. PubMed DOI PMC

Re-appraising the evidence for the source, regulation and function of p53-family isoforms