Multisubunit cullin-RING ubiquitin ligase 4 (CRL4)-DCAF12 recognizes the C-terminal degron containing acidic amino acid residues. However, its physiological roles and substrates are largely unknown. Purification of CRL4-DCAF12 complexes revealed a wide range of potential substrates, including MOV10, an "ancient" RNA-induced silencing complex (RISC) complex RNA helicase. We show that DCAF12 controls the MOV10 protein level via its C-terminal motif in a proteasome- and CRL-dependent manner. Next, we generated Dcaf12 knockout mice and demonstrated that the DCAF12-mediated degradation of MOV10 is conserved in mice and humans. Detailed analysis of Dcaf12-deficient mice revealed that their testes produce fewer mature sperms, phenotype accompanied by elevated MOV10 and imbalance in meiotic markers SCP3 and γ-H2AX. Additionally, the percentages of splenic CD4+ T and natural killer T (NKT) cell populations were significantly altered. In vitro, activated Dcaf12-deficient T cells displayed inappropriately stabilized MOV10 and increased levels of activated caspases. In summary, we identified MOV10 as a novel substrate of CRL4-DCAF12 and demonstrated the biological relevance of the DCAF12-MOV10 pathway in spermatogenesis and T cell activation.

Czech Centre for Phenogenomics Institute of Molecular Genetics of the Czech Academy of Sciences 252 50 Vestec Czech Republic

Faculty of Science Charles University 128 00 Prague Czech Republic

Laboratory of Cancer Biology Institute of Molecular Genetics of the Czech Academy of Sciences 252 42 Vestec Czech Republic

Laboratory of Cell and Developmental Biology Institute of Molecular Genetics of the Czech Academy of Sciences 252 42 Vestec Czech Republic

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Baloghova N., Lidak T., Cermak L. Ubiquitin ligases involved in the regulation of Wnt, TGF-β, and notch signaling pathways and their roles in mouse development and homeostasis. Genes. 2019;10:815. doi: 10.3390/genes10100815. PubMed DOI PMC

Hershko A., Ciechanover A. The ubiquitin system. Annu. Rev. Biochem. 1998;67:425–479. doi: 10.1146/annurev.biochem.67.1.425. PubMed DOI

Skaar J.R., Pagan J.K., Pagano M. Mechanisms and function of substrate recruitment by F-box proteins. Nat. Rev. Mol. Cell Biol. 2013;14:369–381. doi: 10.1038/nrm3582. PubMed DOI PMC

Duan S., Cermak L., Pagan J.K., Rossi M., Martinengo C., di Celle P.F., Chapuy B., Shipp M., Chiarle R., Pagano M. FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature. 2012;481:90–93. doi: 10.1038/nature10688. PubMed DOI PMC

Deshaies R.J., Joazeiro C.A.P. RING domain E3 ubiquitin ligases. Annu. Rev. Biochem. 2009;78:399–434. doi: 10.1146/annurev.biochem.78.101807.093809. PubMed DOI

Sarikas A., Hartmann T., Pan Z.Q. The cullin protein family. Genome Biol. 2011;12:1–12. doi: 10.1186/gb-2011-12-4-220. PubMed DOI PMC

Angers S., Li T., Yi X., MacCoss M.J., Moon R.T., Zheng N. Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Nature. 2006;443:590–593. doi: 10.1038/nature05175. PubMed DOI

Jin J., Arias E.E., Chen J., Harper J.W., Walter J.C. A Family of Diverse Cul4-Ddb1-Interacting Proteins Includes Cdt2, which Is Required for S Phase Destruction of the Replication Factor Cdt1. Mol. Cell. 2006;23:709–721. doi: 10.1016/j.molcel.2006.08.010. PubMed DOI

Higa L.A., Banks D., Wu M., Kobayashi R., Sun H., Zhang H. L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage. Cell Cycle. 2006;5:1675–1680. doi: 10.4161/cc.5.15.3149. PubMed DOI

He Y.J., Mccall C.M., Hu J., Zeng Y., Xiong Y. DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes Dev. 2006:2949–2954. doi: 10.1101/gad.1483206. PubMed DOI PMC

Li T., Robert E.I., van Breugel P.C., Strubin M., Zheng N. A promiscuous α-helical motif anchors viral hijackers and substrate receptors to the CUL4—DDB1 ubiquitin ligase machinery. Nat. Struct. Mol. Biol. 2010;17:105–112. doi: 10.1038/nsmb.1719. PubMed DOI PMC

Reichermeier K.M., Straube R., Reitsma J.M., Sweredoski M.J., Rose C.M., Moradian A., den Besten W., Hinkle T., Verschueren E., Petzold G., et al. PIKES Analysis Reveals Response to Degraders and Key Regulatory Mechanisms of the CRL4 Network. Mol. Cell. 2020;77:1092–1106.e9. doi: 10.1016/j.molcel.2019.12.013. PubMed DOI

Duda D.M., Borg L.A., Scott D.C., Hunt H.W., Hammel M., Schulman B.A. Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation. Cell. 2008;134:995–1006. doi: 10.1016/j.cell.2008.07.022. PubMed DOI PMC

Saha A., Deshaies R.J. Multimodal Activation of the Ubiquitin Ligase SCF by Nedd8 Conjugation. Mol. Cell. 2008;32:21–31. doi: 10.1016/j.molcel.2008.08.021. PubMed DOI PMC

Cavadini S., Fischer E.S., Bunker R.D., Potenza A., Lingaraju G.M., Goldie K.N., Mohamed W.I., Faty M., Petzold G., Beckwith R.E.J., et al. Cullin-RING ubiquitin E3 ligase regulation by the COP9 signalosome. Nature. 2016;531:598–603. doi: 10.1038/nature17416. PubMed DOI

Hwangbo D.S., Biteau B., Rath S., Kim J., Jasper H. Control of apoptosis by Drosophila DCAF12. Dev. Biol. 2016;413:50–59. doi: 10.1016/j.ydbio.2016.03.003. PubMed DOI PMC

Cho Y.S., Li S., Wang X., Zhu J., Zhuo S., Han Y., Yue T., Yang Y., Jiang J. CDK7 regulates organ size and tumor growth by safeguarding the Hippo pathway effector Yki/Yap/Taz in the nucleus. Genes Dev. 2020;34:53–71. doi: 10.1101/gad.333146.119. PubMed DOI PMC

Patrón L.A., Nagatomo K., Eves D.T., Imad M., Young K., Torvund M., Guo X., Rogers G.C., Zinsmaier K.E. Cul4 ubiquitin ligase cofactor DCAF12 promotes neurotransmitter release and homeostatic plasticity. J. Cell Biol. 2019;218:993–1010. doi: 10.1083/jcb.201805099. PubMed DOI PMC

Zou X.D., Hu X.J., Ma J., Li T., Ye Z.Q., Wu Y.D. Genome-wide Analysis of WD40 Protein Family in Human. Sci. Rep. 2016;6:1–11. doi: 10.1038/srep39262. PubMed DOI PMC

Szcześniak M.W., Ciomborowska J., Nowak W., Rogozin I.B., Makałowska I. Primate and rodent specific intron gains and the origin of retrogenes with splice variants. Mol. Biol. Evol. 2011;28:33–37. doi: 10.1093/molbev/msq260. PubMed DOI PMC

Koren I., Timms R.T., Kula T., Xu Q., Li M.Z., Elledge S.J. The Eukaryotic Proteome Is Shaped by E3 Ubiquitin Ligases Targeting C-Terminal Degrons. Cell. 2018;173:1622–1635.e14. doi: 10.1016/j.cell.2018.04.028. PubMed DOI PMC

Ravichandran R., Kodali K., Peng J., Potts P.R. Regulation of MAGE -A3/6 by the CRL 4- DCAF 12 ubiquitin ligase and nutrient availability. EMBO Rep. 2019;20:1–15. doi: 10.15252/embr.201847352. 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

Fairman-Williams M.E., Guenther U.P., Jankowsky E. SF1 and SF2 helicases: Family matters. Curr. Opin. Struct. Biol. 2010;20:313–324. doi: 10.1016/j.sbi.2010.03.011. PubMed DOI PMC

Dalmay T., Horsefield R., Braunstein T.H., Baulcombe D.C. SDE3 encodes an RNA helicase required for post-transcriptional gene silencing in Arabidopsis. EMBO J. 2001;20:2069–2077. doi: 10.1093/emboj/20.8.2069. PubMed DOI PMC

Fischer S.E.J., Butler M.D., Pan Q., Ruvkun G. Trans-splicing in C. elegans generates the negative RNAi regulator ERI-6/7. Nature. 2008;455:491–496. doi: 10.1038/nature07274. PubMed DOI PMC

Fischer S.E.J., Montgomery T.A., Zhang C., Fahlgren N., Breen P.C., Hwang A., Sullivan C.M., Carrington J.C., Ruvkun G. The ERI-6/7 helicase acts at the first stage of an siRNA amplification pathway that targets recent gene duplications. PLoS Genet. 2011;7 doi: 10.1371/journal.pgen.1002369. PubMed DOI PMC

Cook H.A., Koppetsch B.S., Wu J., Theurkauf W.E. The Drosophila SDE3 homolog armitage is required for oskar mRNA silencing and embryonic axis specification. Cell. 2004;116:817–829. doi: 10.1016/S0092-8674(04)00250-8. PubMed DOI

Tomari Y., Du T., Haley B., Schwarz D.S., Bennett R., Cook H.A., Koppetsch B.S., Theurkauf W.E., Zamore P.D. RISC assembly defects in the Drosophila RNAi mutant armitage. Cell. 2004;116:831–841. doi: 10.1016/S0092-8674(04)00218-1. PubMed DOI

Zheng K., Xiol J., Reuter M., Eckardt S., Leu N.L., McLaughlin K.J., Stark A., Sachidanandam R., Pillai R.S., Wang P.J. Mouse MOV10L1 associates with Piwi proteins and is an essential component of the Piwi-interacting RNA (piRNA) pathway. Proc. Natl. Acad. Sci. USA. 2010;107:11841–11846. doi: 10.1073/pnas.1003953107. PubMed DOI PMC

Frost R.J.A., Hamra F.K., Richardson J.A., Qi X., Bassel-Duby R., Olson E.N. MOV10L1 is necessary for protection of spermatocytes against retrotransposons by Piwi-interacting RNAs. Proc. Natl. Acad. Sci. USA. 2010;107:11847–11852. doi: 10.1073/pnas.1007158107. PubMed DOI PMC

Garcia D., Garcia S., Pontier D., Marchais A., Renou J.P., Lagrange T., Voinnet O. Ago Hook and RNA Helicase Motifs Underpin Dual Roles for SDE3 in Antiviral Defense and Silencing of Nonconserved Intergenic Regions. Mol. Cell. 2012;48:109–120. doi: 10.1016/j.molcel.2012.07.028. PubMed DOI

Fischer S.E.J., Ruvkun G. Caenorhabditis elegans ADAR editing and the ERI-6/7/MOV10 RNAi pathway silence endogenous viral elements and LTR retrotransposons. Proc. Natl. Acad. Sci. USA. 2020;117:5987–5996. doi: 10.1073/pnas.1919028117. PubMed DOI PMC

Saito K., Ishizu H., Komai M., Kotani H., Kawamura Y., Nishida K.M., Siomi H., Siomi M.C. Roles for the Yb body components Armitage and Yb in primary piRNA biogenesis in Drosophila. Genes Dev. 2010;24:2493–2498. doi: 10.1101/gad.1989510. PubMed DOI PMC

Arjan-Odedra S., Swanson C.M., Sherer N.M., Wolinsky S.M., Malim M.H. Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses. Retrovirology. 2012;9:1–13. doi: 10.1186/1742-4690-9-53. PubMed DOI PMC

Goodier J.L., Cheung L.E., Kazazian H.H. MOV10 RNA Helicase Is a Potent Inhibitor of Retrotransposition in Cells. PLoS Genet. 2012;8 doi: 10.1371/journal.pgen.1002941. PubMed DOI PMC

Lu C., Luo Z., Jager S., Krogan N.J., Peterlin B.M. Moloney Leukemia Virus Type 10 Inhibits Reverse Transcription and Retrotransposition of Intracisternal A Particles. J. Virol. 2012;86:10517–10523. doi: 10.1128/JVI.00868-12. PubMed DOI PMC

Li X., Zhang J., Jia R., Cheng V., Xu X., Qiao W., Guo F., Liang C., Cen S. The MOV10 helicase inhibits LINE-1 mobility. J. Biol. Chem. 2013;288:21148–21160. doi: 10.1074/jbc.M113.465856. PubMed DOI PMC

Skariah G., Seimetz J., Norsworthy M., Lannom M.C., Kenny P.J., Elrakhawy M., Forsthoefel C., Drnevich J., Kalsotra A., Ceman S. Mov10 suppresses retroelements and regulates neuronal development and function in the developing brain. BMC Biol. 2017;15:1–19. doi: 10.1186/s12915-017-0387-1. PubMed DOI PMC

Choi J., Hwang S.Y., Ahn K. Interplay between RNASEH2 and MOV10 controls LINE-1 retrotransposition. Nucleic Acids Res. 2018;46:1912–1926. doi: 10.1093/nar/gkx1312. PubMed DOI PMC

Warkocki Z., Krawczyk P.S., Adamska D., Bijata K., Garcia-Perez J.L., Dziembowski A. Uridylation by TUT4/7 Restricts Retrotransposition of Human LINE-1s. Cell. 2018;174:1537–1548. doi: 10.1016/j.cell.2018.07.022. PubMed DOI PMC

Burdick R., Smith J.L., Chaipan C., Friew Y., Chen J., Venkatachari N.J., Delviks-Frankenberry K.A., Hu W.-S., Pathak V.K. P Body-Associated Protein Mov10 Inhibits HIV-1 Replication at Multiple Stages. J. Virol. 2010;84:10241–10253. doi: 10.1128/JVI.00585-10. PubMed DOI PMC

Wang X., Han Y., Dang Y., Fu W., Zhou T., Ptak R.G., Zheng Y.H. Moloney leukemia virus 10 (MOV10) protein inhibits retrovirus replication. J. Biol. Chem. 2010;285:14346–14355. doi: 10.1074/jbc.M110.109314. PubMed DOI PMC

Furtak V., Mulky A., Rawlings S.A., Kozhaya L., Lee K.E., KewalRamani V.N., Unutmaz D. Perturbation of the P-body component Mov10 inhibits HIV-1 infectivity. PLoS ONE. 2010;5 doi: 10.1371/journal.pone.0009081. PubMed DOI PMC

Abudu A., Wang X., Dang Y., Zhou T., Xiang S.H., Zheng Y.H. Identification of molecular determinants from Moloney leukemia virus 10 homolog (MOV10) protein for virion packaging and anti-HIV-1 activity. J. Biol. Chem. 2012;287:1220–1228. doi: 10.1074/jbc.M111.309831. PubMed DOI PMC

Schoggins J.W., Wilson S.J., Panis M., Murphy M.Y., Jones C.T., Bieniasz P., Rice C.M. A diverse range of gene products are effectors of the type i interferon antiviral response. Nature. 2011;472:481–485. doi: 10.1038/nature09907. PubMed DOI PMC

Shaw A.E., Hughes J., Gu Q., Behdenna A., Singer J.B., Dennis T., Orton R.J., Varela M., Gifford R.J., Wilson S.J., et al. Fundamental properties of the mammalian innate immune system revealed by multispecies comparison of type I interferon responses. PLoS Biol. 2017;15:1–23. doi: 10.1371/journal.pbio.2004086. PubMed DOI PMC

Cuevas R.A., Ghosh A., Wallerath C., Hornung V., Coyne C.B., Sarkar S.N. MOV10 Provides Antiviral Activity against RNA Viruses by Enhancing RIG-I–MAVS-Independent IFN Induction. J. Immunol. 2016;196:3877–3886. doi: 10.4049/jimmunol.1501359. PubMed DOI PMC

Liu D., Ndongwe T.P., Puray-Chavez M., Casey M.C., Izumi T., Pathak V.K., Tedbury P.R., Sarafianos S.G. Effect of P-body component Mov10 on HCV virus production and infectivity. FASEB J. 2020;34:9433–9449. doi: 10.1096/fj.201800641R. PubMed DOI PMC

Zhang J., Huang F., Tan L., Bai C., Chen B., Liu J., Liang J., Liu C., Zhang S., Lu G., et al. Host Protein Moloney Leukemia Virus 10 (MOV10) Acts as a Restriction Factor of Influenza A Virus by Inhibiting the Nuclear Import of the Viral Nucleoprotein. J. Virol. 2016;90:3966–3980. doi: 10.1128/JVI.03137-15. PubMed DOI PMC

Li J., Hu S., Xu F., Mei S., Liu X., Yin L., Zhao F., Zhao X., Sun H., Xiong Z., et al. MOV10 sequesters the RNP of influenza A virus in the cytoplasm and is antagonized by viral NS1 protein. Biochem. J. 2019;476:467–481. doi: 10.1042/BCJ20180754. PubMed DOI

Mo Q., Xu Z., Deng F., Wang H., Ning Y.J. Host restriction of emerging high-pathogenic bunyaviruses via MOV10 by targeting viral nucleoprotein and blocking ribonucleoprotein assembly. PLoS Pathog. 2020;16:1–30. doi: 10.1371/journal.ppat.1009129. PubMed DOI PMC

Haussecker D., Cao D., Huang Y., Parameswaran P., Fire A.Z., Kay M.A. Capped small RNAs and MOV10 in Human Hepatitis Delta Virus replicatio. Nat. Struct. Mol. Biol. 2008;15:714–721. doi: 10.1038/nsmb.1440. PubMed DOI PMC

Liu T., Sun Q., Liu Y., Cen S., Zhang Q. The MOV10 helicase restricts hepatitis B virus replication by inhibiting viral reverse transcription. J. Biol. Chem. 2019;294:19804–19813. doi: 10.1074/jbc.RA119.009435. PubMed DOI PMC

Puray-Chavez M.N., Farghali M.H., Yapo V., Huber A.D., Liu D., Ndongwe T.P., Casey M.C., Laughlin T.G., Hannink M., Tedbury P.R., et al. Effects of moloney leukemia virus 10 protein on hepatitis B virus infection and viral replication. Viruses. 2019;11:651. doi: 10.3390/v11070651. PubMed DOI PMC

Meister G., Landthaler M., Peters L., Chen P.Y., Urlaub H., Lührmann R., Tuschl T. Identification of novel argonaute-associated proteins. Curr. Biol. 2005;15:2149–2155. doi: 10.1016/j.cub.2005.10.048. PubMed DOI

Chendrimada T.P., Finn K.J., Ji X., Baillat D., Gregory R.I., Liebhaber S.A., Pasquinelli A.E., Shiekhattar R. MicroRNA silencing through RISC recruitment of eIF6. Nature. 2007;447:823–828. doi: 10.1038/nature05841. PubMed DOI

Liu C., Zhang X., Huang F., Yang B., Li J., Liu B., Luo H., Zhang P., Zhang H. APOBEC3G inhibits microRNA-mediated repression of translation by interfering with the interaction between Argonaute-2 and MOV10. J. Biol. Chem. 2012;287:29373–29383. doi: 10.1074/jbc.M112.354001. PubMed DOI PMC

Kenny P.J., Zhou H., Kim M., Skariah G., Khetani R.S., Drnevich J., Arcila M.L., Kosik K.S., Ceman S. MOV10 and FMRP Regulate AGO2 Association with MicroRNA Recognition Elements. Cell Rep. 2014;9:1729–1741. doi: 10.1016/j.celrep.2014.10.054. PubMed DOI PMC

Fu K., Tian S., Tan H., Wang C., Wang H., Wang M., Wang Y., Chen Z., Wang Y., Yue Q., et al. Biological and RNA regulatory function of MOV10 in mammalian germ cells. BMC Biol. 2019;17:1–24. doi: 10.1186/s12915-019-0659-z. PubMed DOI PMC

Gregersen L.H., Schueler M., Munschauer M., Mastrobuoni G., Chen W., Kempa S., Dieterich C., Landthaler M. MOV10 Is a 5′ to 3′ RNA Helicase Contributing to UPF1 mRNA Target Degradation by Translocation along 3′ UTRs. Mol. Cell. 2014;54:573–585. doi: 10.1016/j.molcel.2014.03.017. PubMed DOI

Messaoudi-Aubert S.E.L., Nicholls J., Maertens G.N., Brookes S., Bernstein E., Peters G. Role for the MOV10 RNA helicase in Polycomb-mediated repression of the INK4a tumor suppressor. Nat. Struct. Mol. Biol. 2010;17:862–868. doi: 10.1038/nsmb.1824. PubMed DOI PMC

Wang Y., Wang W., Xu L., Zhou X., Shokrollahi E., Felczak K., van der Laan L.J.W., Pankiewicz K.W., Sprengers D., Raat N.J.H., et al. Cross Talk between Nucleotide Synthesis Pathways with Cellular Immunity in Constraining Hepatitis E Virus Replication. Antimicrob. Agents Chemother. 2016;60:2834–2848. doi: 10.1128/AAC.02700-15. PubMed DOI PMC

Latour S., Aguilar C. XIAP deficiency syndrome in humans. Semin. Cell Dev. Biol. 2015;39:115–123. doi: 10.1016/j.semcdb.2015.01.015. PubMed DOI

Pujantell M., Riveira-Muñoz E., Badia R., Castellví M., Garcia-Vidal E., Sirera G., Puig T., Ramirez C., Clotet B., Esté J.A., et al. RNA editing by ADAR1 regulates innate and antiviral immune functions in primary macrophages. Sci. Rep. 2017;7:1–14. doi: 10.1038/s41598-017-13580-0. PubMed DOI PMC

Madeira F., Park Y.M., Lee J., Buso N., Gur T., Madhusoodanan N., Basutkar P., Tivey A.R.N., Potter S.C., Finn R.D., et al. The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucleic Acids Res. 2019;47:W636–W641. doi: 10.1093/nar/gkz268. PubMed DOI PMC

Han X., Wang R., Zhou Y., Fei L., Sun H., Lai S., Saadatpour A., Zhou Z., Chen H., Ye F., et al. Mapping the Mouse Cell Atlas by Microwell-Seq. Cell. 2018;172:1091–1107. doi: 10.1016/j.cell.2018.02.001. PubMed DOI

Yukawa M., Jagannathan S., Kartashov A.V., Chen X., Weirauch M.T., Barski A. Co-Stimulation–Induced AP-1 Activity is Required for Chromatin Opening During T Cell Activation. bioRxiv. 2019 doi: 10.1084/jem.20182009. PubMed DOI PMC

White C.H., Moesker B., Beliakova-Bethell N., Martins L.J., Spina C.A., Margolis D.M., Richman D.D., Planelles V., Bosque A., Woelk C.H. Transcriptomic Analysis Implicates the p53 Signaling Pathway in the Establishment of HIV-1 Latency in Central Memory CD4 T Cells in an In Vitro Model. PLoS Pathog. 2016;12:1–23. doi: 10.1371/journal.ppat.1006026. PubMed DOI PMC

Man K., Miasari M., Shi W., Xin A., Henstridge D.C., Preston S., Pellegrini M., Belz G.T., Smyth G.K., Febbraio M.A., et al. The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells. Nat. Immunol. 2013;14:1155–1165. doi: 10.1038/ni.2710. PubMed DOI

Yeh C., Huang W., Hsu P., Yeh K., Wang L., Hsu P.W., Lin H., Chen Y., Chen S., Yeang C., et al. The C-degron pathway eliminates mislocalized proteins and products of deubiquitinating enzymes. EMBO J. 2021:1–20. doi: 10.15252/embj.2020105846. PubMed DOI PMC

Hornbeck P.V., Zhang B., Murray B., Kornhauser J.M., Latham V., Skrzypek E. PhosphoSitePlus, 2014: Mutations, PTMs and recalibrations. Nucleic Acids Res. 2015;43:D512–D520. doi: 10.1093/nar/gku1267. PubMed DOI PMC

Mertins P., Qiao J.W., Patel J., Udeshi N.D., Clauser K.R., Mani D.R., Burgess M.W., Gillette M.A., Jaffe J.D., Carr S.A. Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat. Methods. 2013;10:634–637. doi: 10.1038/nmeth.2518. PubMed DOI PMC

Bouhaddou M., Memon D., Meyer B., White K.M., Rezelj V.V., Correa Marrero M., Polacco B.J., Melnyk J.E., Ulferts S., Kaake R.M., et al. The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020;182:685–712.e19. doi: 10.1016/j.cell.2020.06.034. PubMed DOI PMC

Yang J.Y., Humphrey S.J., Yang G., Yang P., Fazakerley D.J., Sto J., James D.E. Resource Dynamic Adipocyte Phosphoproteome Reveals that Akt Directly Regulates mTORC2. Cell Metabol. 2013:1009–1020. doi: 10.1016/j.cmet.2013.04.010. PubMed DOI PMC

Cai L., Liu L., Li L., Jia L. SCFFBXO28-mediated self-ubiquitination of FBXO28 promotes its degradation. Cell. Signal. 2020;65:109440. doi: 10.1016/j.cellsig.2019.109440. PubMed DOI

De Bie P., Ciechanover A. Ubiquitination of E3 ligases: Self-regulation of the ubiquitin system via proteolytic and non-proteolytic mechanisms. Cell Death Differ. 2011;18:1393–1402. doi: 10.1038/cdd.2011.16. PubMed DOI PMC

Rossi M., Duan S., Jeong Y.T., Horn M., Saraf A., Florens L., Washburn M.P., Antebi A., Pagano M. Regulation of the CRL4Cdt2ubiquitin ligase and Cell-Cycle exit by the SCFFbxo11ubiquitin ligase. Mol. Cell. 2013;49:1159–1166. doi: 10.1016/j.molcel.2013.02.004. PubMed DOI PMC

Fernandez-Capetillo O., Mahadevaiah S.K., Celeste A., Romanienko P.J., Camerini-Otero R.D., Bonner W.M., Manova K., Burgoyne P., Nussenzweig A. H2AX is required for chromatin remodeling and inactivation of sex chromosomes in male mouse meiosis. Dev. Cell. 2003;4:497–508. doi: 10.1016/S1534-5807(03)00093-5. PubMed DOI

Yuan L., Liu J.G., Zhao J., Brundell E., Daneholt B., Höög C. The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol. Cell. 2000;5:73–83. doi: 10.1016/S1097-2765(00)80404-9. PubMed DOI

Modzelewski A.J., Hilz S., Crate E.A., Schweidenback C.T.H., Fogarty E.A., Grenier J.K., Freire R., Cohen P.E., Grimson A. Dgcr8 and Dicer are essential for sex chromosome integrity during meiosis in males. J. Cell Sci. 2015;128:2314–2327. doi: 10.1242/jcs.167148. PubMed DOI PMC

Zimmermann C., Romero Y., Warnefors M., Bilican A., Borel C., Smith L.B., Kotaja N., Kaessmann H., Nef S. Germ cell-specific targeting of DICER or DGCR8 reveals a novel role for endo-siRNAs in the progression of mammalian spermatogenesis and male fertility. PLoS ONE. 2014;9 doi: 10.1371/journal.pone.0107023. PubMed DOI PMC

Chen X., Li X., Guo J., Zhang P., Zeng W. The roles of microRNAs in regulation of mammalian spermatogenesis. J. Anim. Sci. Biotechnol. 2017;8:1–8. doi: 10.1186/s40104-017-0166-4. PubMed DOI PMC

Sakashita A., Maezawa S., Takahashi K., Alavattam K.G., Yukawa M., Hu Y.C., Kojima S., Parrish N.F., Barski A., Pavlicev M., et al. Endogenous retroviruses drive species-specific germline transcriptomes in mammals. Nat. Struct. Mol. Biol. 2020;27:967–977. doi: 10.1038/s41594-020-0487-4. PubMed DOI PMC

Podshivalova K., Salomon D.R. MicroRNA regulation of T-lymphocyte immunity: Modulation of molecular networks responsible for T-cell activation, differentiation, and development. Crit. Rev. Immunol. 2013;33:435–476. doi: 10.1615/CritRevImmunol.2013006858. PubMed DOI PMC

O’Connell R.M., Rao D.S., Chaudhuri A.A., Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat. Rev. Immunol. 2010;10:111–122. doi: 10.1038/nri2708. PubMed DOI

Muljo S.A., Mark Ansel K., Kanellopoulou C., Livingston D.M., Rao A., Rajewsky K. Aberrant T cell differentiation in the absence of Dicer. J. Exp. Med. 2005;202:261–269. doi: 10.1084/jem.20050678. PubMed DOI PMC

Cobb B.S., Nesterova T.B., Thompson E., Hertweck A., O’Connor E., Godwin J., Wilson C.B., Brockdorff N., Fisher A.G., Smale S.T., et al. T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer. J. Exp. Med. 2005;201:1367–1373. doi: 10.1084/jem.20050572. PubMed DOI PMC

Chong M.M.W., Rasmussen J.P., Rudensky A.Y., Littman D.R. The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease. J. Exp. Med. 2008;205:2005–2017. doi: 10.1084/jem.20081219. PubMed DOI PMC

Bronevetsky Y., Villarino A.V., Eisley C.J., Barbeau R., Barczak A.J., Heinz G.A., Kremmer E., Heissmeyer V., McManus M.T., Erle D.J., et al. T cell activation induces proteasomal degradation of argonaute and rapid remodeling of the microRNA repertoire. J. Exp. Med. 2013;210:417–432. doi: 10.1084/jem.20111717. PubMed DOI PMC

Grigoryev Y.A., Kurian S.M., Hart T., Nakorchevsky A.A., Chen C., Campbell D., Head S.R., Yates J.R., Salomon D.R. MicroRNA Regulation of Molecular Networks Mapped by Global MicroRNA, mRNA, and Protein Expression in Activated T Lymphocytes. J. Immunol. 2011;187:2233–2243. doi: 10.4049/jimmunol.1101233. PubMed DOI PMC

Gutiérrez-Vázquez C., Rodríguez-Galán A., Fernández-Alfara M., Mittelbrunn M., Sánchez-Cabo F., Martínez-Herrera D.J., Ramírez-Huesca M., Pascual-Montano A., Sánchez-Madrid F. MiRNA profiling during antigen-dependent T cell activation: A role for miR-132-3p. Sci. Rep. 2017;7:3–10. doi: 10.1038/s41598-017-03689-7. PubMed DOI PMC

Ye M., Goudot C., Hoyler T., Lemoine B., Amigorena S., Zueva E. Specific subfamilies of transposable elements contribute to different domains of T lymphocyte enhancers. Proc. Natl. Acad. Sci. USA. 2020;117:7905–7916. doi: 10.1073/pnas.1912008117. PubMed DOI PMC

Tokuyama M., Kong Y., Song E., Jayewickreme T., Kang I., Iwasaki A. ERVmap analysis reveals genome-wide transcription of human endogenous retroviruses. Proc. Natl. Acad. Sci. USA. 2018;115:12565–12572. doi: 10.1073/pnas.1814589115. PubMed DOI PMC

Young G.R., Eksmond U., Salcedo R., Alexopoulou L., Stoye J.P., Kassiotis G. Resurrection of endogenous retroviruses in antibody-deficient mice. Nature. 2012;491:774–778. doi: 10.1038/nature11599. PubMed DOI PMC

Bosque A., Planelles V. Induction of HIV-1 latency and reactivation in primary memory CD4+ T cells. Blood. 2009;113:58–65. doi: 10.1182/blood-2008-07-168393. PubMed DOI PMC

Novis C.L., Archin N.M., Buzon M.J., Verdin E., Round J.L., Lichterfeld M., Margolis D.M., Planelles V., Bosque A. Reactivation of latent HIV-1 in central memory CD4+ T cells through TLR-1/2 stimulation. Retrovirology. 2013;10:1–15. doi: 10.1186/1742-4690-10-119. PubMed DOI PMC

Christakoudi S., Runglall M., Mobillo P., Tsui T.L., Duff C., Domingo-Vila C., Kamra Y., Delaney F., Montero R., Spiridou A., et al. Development of a multivariable gene-expression signature targeting T-cell-mediated rejection in peripheral blood of kidney transplant recipients validated in cross-sectional and longitudinal samples. EBioMedicine. 2019;41:571–583. doi: 10.1016/j.ebiom.2019.01.060. PubMed DOI PMC

Bakir M., Jackson N.J., Han S.X., Bui A., Chang E., Liem D.A., Ardehali A., Ardehali R., Baas A.S., Press M.C., et al. Clinical phenomapping and outcomes after heart transplantation. J. Hear. Lung Transplant. 2018;37:956–966. doi: 10.1016/j.healun.2018.03.006. PubMed DOI PMC

Kim S.W., Jung Y.S., Ahn J.B., Shin E.S., Jang H.W., Lee H.J., Il Kim T., Kim D.Y., Bang D., Kim W.H., et al. Identification of genetic susceptibility loci for intestinal Behçet’s disease. Sci. Rep. 2017;7:39850. doi: 10.1038/srep39850. PubMed DOI PMC

Gloeckner C.J., Boldt K., Schumacher A., Ueffing M. Proteomics. Humana Press; Totowa, NJ, USA: 2009. Tandem Affinity Purification of Protein Complexes from Mammalian Cells by the Strep/FLAG (SF)-TAP Tag; pp. 359–372. PubMed

Chen S., Lee B., Lee A.Y.F., Modzelewski A.J., He L. Highly efficient mouse genome editing by CRISPR ribonucleoprotein electroporation of zygotes. J. Biol. Chem. 2016;291:14457–14467. doi: 10.1074/jbc.M116.733154. PubMed DOI PMC

Sanjana N.E., Shalem O., Zhang F. Improved vectors and genome-wide libraries for CRISPR screening. Nat. Methods. 2014;11:783–784. doi: 10.1038/nmeth.3047. PubMed DOI PMC

Tandon N., Thakkar K., LaGory E., Liu Y., Giaccia A. Generation of Stable Expression Mammalian Cell Lines Using Lentivirus. Bio-Protocol. 2018;8:8–13. doi: 10.21769/BioProtoc.3073. PubMed DOI PMC

Kowarz E., Löscher D., Marschalek R. Optimized Sleeping Beauty transposons rapidly generate stable transgenic cell lines. Biotechnol. J. 2015;10:647–653. doi: 10.1002/biot.201400821. PubMed DOI

Durkin M.E., Qian X., Popescu N.C., Lowy D.R. Isolation of Mouse Embryo Fibroblasts. Bio-Protocol. 2013;3:100–106. doi: 10.21769/BioProtoc.908. PubMed DOI PMC

Kamijo T., Zindy F., Roussel M.F., Quelle D.E., Downing J.R., Ashmun R.A., Grosveld G., Sherr C.J. Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19(ARF) Cell. 1997;91:649–659. doi: 10.1016/S0092-8674(00)80452-3. PubMed DOI

Longo P.A., Kavran J.M., Kim M.-S., Leahy D.J. Transient mammalian cell transfection with polyethylenimine (PEI) Methods Enzymol. 2013;529:227–240. doi: 10.1016/B978-0-12-418687-3.00018-5. PubMed DOI PMC

International Mouse Phenotyping Consortium Immunophenotyping. [(accessed on 24 April 2021)]; Available online: https://www.mousephenotype.org/impress/ProcedureInfo?action=list&procID=1225&pipeID=7.

FBXO38 Ubiquitin Ligase Controls Centromere Integrity via ZXDA/B Stability