Epitranscriptomic Regulations in the Heart
Jazyk angličtina Země Česko Médium print-electronic
Typ dokumentu časopisecké články, přehledy
PubMed
38634649
PubMed Central
PMC11412340
DOI
10.33549/physiolres.935265
PII: 935265
Knihovny.cz E-zdroje
- MeSH
- adenosin analogy a deriváty metabolismus MeSH
- epigeneze genetická * MeSH
- lidé MeSH
- myokard metabolismus MeSH
- posttranskripční úpravy RNA MeSH
- transkriptom MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- adenosin MeSH
RNA modifications affect key stages of the RNA life cycle, including splicing, export, decay, and translation. Epitranscriptomic regulations therefore significantly influence cellular physiology and pathophysiology. Here, we selected some of the most abundant modifications and reviewed their roles in the heart and in cardiovascular diseases: N6-methyladenosine (m6A), N6,2'-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), pseudouridine (?), 5 methylcytidine (m5C), and inosine (I). Dysregulation of epitranscriptomic machinery affecting these modifications vastly changes the cardiac phenotype and is linked with many cardiovascular diseases such as myocardial infarction, cardiomyopathies, or heart failure. Thus, a deeper understanding of these epitranscriptomic changes and their regulatory mechanisms can enhance our knowledge of the molecular underpinnings of prevalent cardiac diseases, potentially paving the way for novel therapeutic strategies. Keywords: Epitranscriptomics, RNA modifications, Epigenetics, m6A, RNA, Heart.
Zobrazit více v PubMed
Crick FH. On protein synthesis. Symp Soc Exp Biol. 1958;12:138–163. PubMed
Devaux Y, Robinson EL. Preface. In: Devaux Y, Robinson EL, editors. Epigenetics in Cardiovascular Disease. Academic Press; 2021. pp. XXI–XXVI. DOI
Zhang L, Lu Q, Chang C. Epigenetics in Health and Disease. In: Chang C, Lu Q, editors. Epigenetics in Allergy and Autoimmunity. Singapore: Springer Singapore; 2020. pp. 3–55. DOI
Boccaletto P, Machnicka MA, Purta E, Piatkowski P, Baginski B, Wirecki TK, de Crécy-Lagard V, Ross R, Limbach PA, Kotter A, Helm M, Bujnicki JM. MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Res. 2018;46:D303–d307. doi: 10.1093/nar/gkx1030. PubMed DOI PMC
Roundtree IA, Evans ME, Pan T, He C. Dynamic RNA Modifications in Gene Expression Regulation. Cell. 2017;169:1187–1200. doi: 10.1016/j.cell.2017.05.045. PubMed DOI PMC
Dieterich C, Völkers M. Chapter 6 - RNA modifications in cardiovascular disease-An experimental and computational perspective. In: Devaux Y, Robinson EL, editors. Epigenetics in Cardiovascular Disease. Academic Press; 2021. pp. 113–125. DOI
Lee Y, Choe J, Park OH, Kim YK. Molecular Mechanisms Driving mRNA Degradation by m(6)A Modification. Trends Genet. 2020;36:177–188. doi: 10.1016/j.tig.2019.12.007. PubMed DOI
Boo SH, Kim YK. The emerging role of RNA modifications in the regulation of mRNA stability. Exp Mol Med. 2020;52:400–408. doi: 10.1038/s12276-020-0407-z. PubMed DOI PMC
Desrosiers R, Friderici K, Rottman F. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc Natl Acad Sci U S A. 1974;71:3971–3975. doi: 10.1073/pnas.71.10.3971. PubMed DOI PMC
Dominissini D, Moshitch-Moshkovitz S, Salmon-Divon M, Amariglio N, Rechavi G. Transcriptome-wide mapping of N(6)-methyladenosine by m(6)A-seq based on immunocapturing and massively parallel sequencing. Nat Protoc. 2013;8:176–189. doi: 10.1038/nprot.2012.148. PubMed DOI
Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR. Comprehensive analysis of mRNA methylation reveals enrichment in 3’ UTRs and near stop codons. Cell. 2012;149:1635–1646. doi: 10.1016/j.cell.2012.05.003. PubMed DOI PMC
Oerum S, Meynier V, Catala M, Tisné C. A comprehensive review of m6A/m6Am RNA methyltransferase structures. Nucleic Acids Res. 2021;49:7239–7255. doi: 10.1093/nar/gkab378. PubMed DOI PMC
Wang P, Doxtader KA, Nam Y. Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases. Mol Cell. 2016;63:306–317. doi: 10.1016/j.molcel.2016.05.041. PubMed DOI PMC
Wang X, Feng J, Xue Y, Guan Z, Zhang D, Liu Z, Gong Z, Wang Q, Huang J, Tang C, Zou T, Yin P. Structural basis of N(6)-adenosine methylation by the METTL3–METTL14 complex. Nature. 2016;534:575–578. doi: 10.1038/nature18298. PubMed DOI
Zheng G, Dahl JA, Niu Y, Fedorcsak P, Huang CM, Li CJ, Vågbø CB, Shi Y, Wang WL, Song SH, Lu Z, Bosmans RP, Dai Q, Hao YJ, Yang X, Zhao WM, Tong WM, Wang XJ, Bogdan F, Furu K, Fu Y, Jia G, Zhao X, Liu J, Krokan HE, Klungland A, Yang YG, He C. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell. 2013;49:18–29. doi: 10.1016/j.molcel.2012.10.015. PubMed DOI PMC
Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, Yi C, Lindahl T, Pan T, Yang YG, He C. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol. 2011;7:885–887. doi: 10.1038/nchembio.687. PubMed DOI PMC
Wei J, Liu F, Lu Z, Fei Q, Ai Y, He PC, Shi H, Cui X, Su R, Klungland A, Jia G, Chen J, He C. Differential m(6)A, m(6)A(m), and m(1)A Demethylation Mediated by FTO in the Cell Nucleus and Cytoplasm. Mol Cell. 2018;71:973–985.e975. doi: 10.1016/j.molcel.2018.08.011. PubMed DOI PMC
Relier S, Ripoll J, Guillorit H, Amalric A, Achour C, Boissière F, Vialaret J, Attina A, Debart F, Choquet A, Macari F, Marchand V, Motorin Y, Samalin E, Vasseur JJ, Pannequin J, Aguilo F, Lopez-Crapez E, Hirtz C, Rivals E, Bastide A, David A. FTO-mediated cytoplasmic m(6)A(m) demethylation adjusts stem-like properties in colorectal cancer cell. Nat Commun. 2021;12:1716. doi: 10.1038/s41467-021-21758-4. PubMed DOI PMC
Zaccara S, Jaffrey SR. A Unified Model for the Function of YTHDF Proteins in Regulating m(6)A-Modified mRNA. Cell. 2020;181:1582–1595.e1518. doi: 10.1016/j.cell.2020.05.012. PubMed DOI PMC
Lasman L, Krupalnik V, Viukov S, Mor N, Aguilera-Castrejon A, Schneir D, Bayerl J, Mizrahi O, Peles S, Tawil S, Sathe S, Nachshon A, Shani T, Zerbib M, Kilimnik I, Aigner S, Shankar A, Mueller JR, Schwartz S, Stern-Ginossar N, Yeo GW, Geula S, Novershtern N, Hanna JH. Context-dependent functional compensation between Ythdf m(6)A reader proteins. Genes Dev. 2020;34:1373–1391. doi: 10.1101/gad.340695.120. PubMed DOI PMC
Wang X, Lu Z, Gomez A, Hon GC, Yue Y, Han D, Fu Y, Parisien M, Dai Q, Jia G, Ren B, Pan T, He C. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature. 2014;505:117–120. doi: 10.1038/nature12730. PubMed DOI PMC
Wang X, Zhao BS, Roundtree IA, Lu Z, Han D, Ma H, Weng X, Chen K, Shi H, He C. N(6)-methyladenosine Modulates Messenger RNA Translation Efficiency. Cell. 2015;161:1388–1399. doi: 10.1016/j.cell.2015.05.014. PubMed DOI PMC
Xiao W, Adhikari S, Dahal U, Chen YS, Hao YJ, Sun BF, Sun HY, Li A, Ping XL, Lai WY, Wang X, Ma HL, Huang CM, Yang Y, Huang N, Jiang GB, Wang HL, Zhou Q, Wang XJ, Zhao YL, Yang YG. Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing. Mol Cell. 2016;61:507–519. https://doi.org/10.1016/j.molcel.2016.01.012, https://doi.org/10.1016/j.molcel.2016.03.004. PubMed DOI
Hsu PJ, Zhu Y, Ma H, Guo Y, Shi X, Liu Y, Qi M, Lu Z, Shi H, Wang J, Cheng Y, Luo G, Dai Q, Liu M, Guo X, Sha J, Shen B, He C. Ythdc2 is an N(6)-methyladenosine binding protein that regulates mammalian spermatogenesis. Cell Res. 2017;27:1115–1127. doi: 10.1038/cr.2017.99. PubMed DOI PMC
Shi H, Wang X, Lu Z, Zhao BS, Ma H, Hsu PJ, Liu C, He C. YTHDF3 facilitates translation and decay of N(6)-methyladenosine-modified RNA. Cell Res. 2017;27:315–328. doi: 10.1038/cr.2017.15. PubMed DOI PMC
Liu XH, Liu Z, Ren ZH, Chen HX, Zhang Y, Zhang Z, Cao N, Luo GZ. Co-effects of m6A and chromatin accessibility dynamics in the regulation of cardiomyocyte differentiation. Epigenetics Chromatin. 2023;16:32. doi: 10.1186/s13072-023-00506-6. PubMed DOI PMC
Han Z, Wang X, Xu Z, Cao Y, Gong R, Yu Y, Yu Y, Guo X, Liu S, Yu M, Ma W, Zhao Y, Xu J, Li X, Li S, Xu Y, Song R, Xu B, Yang F, Bamba D, Sukhareva N, Lei H, Gao M, Zhang W, Zagidullin N, Zhang Y, Yang B, Pan Z, Cai B. ALKBH5 regulates cardiomyocyte proliferation and heart regeneration by demethylating the mRNA of YTHDF1. Theranostics. 2021;11:3000–3016. doi: 10.7150/thno.47354. PubMed DOI PMC
Yang C, Zhao K, Zhang J, Wu X, Sun W, Kong X, Shi J. Comprehensive Analysis of the Transcriptome-Wide m6A Methylome of Heart via MeRIP After Birth: Day 0 vs. Day 7. Front Cardiovasc Med. 2021;8:633631. doi: 10.3389/fcvm.2021.633631. PubMed DOI PMC
Semenovykh D, Benak D, Holzerova K, Cerna B, Telensky P, Vavrikova T, Kolar F, Neckar J, Hlavackova M. Myocardial m6A regulators in postnatal development: effect of sex. Physiol Res. 2022;71:877–882. doi: 10.33549/physiolres.934970. PubMed DOI PMC
Boissel S, Reish O, Proulx K, Kawagoe-Takaki H, Sedgwick B, Yeo GS, Meyre D, Golzio C, Molinari F, Kadhom N, Etchevers HC, Saudek V, Farooqi IS, Froguel P, Lindahl T, O’Rahilly S, Munnich A, Colleaux L. Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am J Hum Genet. 2009;85:106–111. doi: 10.1016/j.ajhg.2009.06.002. PubMed DOI PMC
Liu C, Mou S, Pan C. The FTO gene rs9939609 polymorphism predicts risk of cardiovascular disease: a systematic review and meta-analysis. PLoS One. 2013;8:e71901. doi: 10.1371/journal.pone.0071901. PubMed DOI PMC
Doney AS, Dannfald J, Kimber CH, Donnelly LA, Pearson E, Morris AD, Palmer CN. The FTO gene is associated with an atherogenic lipid profile and myocardial infarction in patients with type 2 diabetes: a Genetics of Diabetes Audit and Research Study in Tayside Scotland (Go-DARTS) study. Circ Cardiovasc Genet. 2009;2:255–259. doi: 10.1161/CIRCGENETICS.108.822320. PubMed DOI PMC
Hubacek JA, Vrablik M, Dlouha D, Stanek V, Gebauerova M, Adamkova V, Ceska R, Dostálová G, Linhart A, Vitek L, Pitha J. Gene variants at FTO, 9p21, and 2q36.3 are age-independently associated with myocardial infarction in Czech men. Clin Chim Acta. 2016;454:119–123. doi: 10.1016/j.cca.2016.01.005. PubMed DOI
Hubacek JA, Stanek V, Gebauerová M, Pilipcincová A, Dlouhá D, Poledne R, Aschermann M, Skalická H, Matousková J, Kruger A, Penicka M, Hrabáková H, Veselka J, Hájek P, Lánská V, Adámková V, Pitha J. A FTO variant and risk of acute coronary syndrome. Clin Chim Acta. 2010;411:1069–1072. doi: 10.1016/j.cca.2010.03.037. PubMed DOI
Hubacek JA, Vymetalova J, Lanska V, Dlouha D. The fat mass and obesity related gene polymorphism influences the risk of rejection in heart transplant patients. Clin Transplant. 2018;32:e13443. doi: 10.1111/ctr.13443. PubMed DOI
Zhen X, Zhao W, Wang J, Li L, He Y, Zhang J, Li C, Zhang S, Huang J, Luo B, Gao Y. Genetic variations within METTL16 and susceptibility to sudden cardiac death in chinese populations with coronary artery disease. Am J Cardiol. 2023;202:90–99. doi: 10.1016/j.amjcard.2023.06.062. PubMed DOI
Wakil SM, Ram R, Muiya NP, Mehta M, Andres E, Mazhar N, Baz B, Hagos S, Alshahid M, Meyer BF, Morahan G, Dzimiri N. A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs. Atherosclerosis. 2016;245:62–70. doi: 10.1016/j.atherosclerosis.2015.11.019. PubMed DOI
Zhang R, Qu Y, Ji Z, Hao C, Su Y, Yao Y, Zuo W, Chen X, Yang M, Ma G. METTL3 mediates Ang-II-induced cardiac hypertrophy through accelerating pri-miR-221/222 maturation in an m6A-dependent manner. Cell Mol Biol Lett. 2022;27:55. doi: 10.1186/s11658-022-00349-1. PubMed DOI PMC
Carnevali L, Graiani G, Rossi S, Al Banchaabouchi M, Macchi E, Quaini F, Rosenthal N, Sgoifo A. Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice. PLoS One. 2014;9:e95499. doi: 10.1371/journal.pone.0095499. PubMed DOI PMC
Gan XT, Zhao G, Huang CX, Rowe AC, Purdham DM, Karmazyn M. Identification of fat mass and obesity associated (FTO) protein expression in cardiomyocytes: regulation by leptin and its contribution to leptin-induced hypertrophy. PLoS One. 2013;8:e74235. doi: 10.1371/journal.pone.0074235. PubMed DOI PMC
Dorn LE, Lasman L, Chen J, Xu X, Hund TJ, Medvedovic M, Hanna JH, van Berlo JH, Accornero F. The N(6)-methyladenosine mRNA methylase METTL3 controls cardiac homeostasis and hypertrophy. Circulation. 2019;139:533–545. doi: 10.1161/CIRCULATIONAHA.118.036146. PubMed DOI PMC
Kmietczyk V, Riechert E, Kalinski L, Boileau E, Malovrh E, Malone B, Gorska A, Hofmann C, Varma E, Jürgensen L, Kamuf-Schenk V, Altmüller J, Tappu R, Busch M, Most P, Katus HA, Dieterich C, Völkers M. m(6)A-mRNA methylation regulates cardiac gene expression and cellular growth. Life Sci Alliance. 2019;2:e201800233. doi: 10.26508/lsa.201800233. PubMed DOI PMC
Mathiyalagan P, Adamiak M, Mayourian J, Sassi Y, Liang Y, Agarwal N, Jha D, Zhang S, Kohlbrenner E, Chepurko E, Chen J, Trivieri MG, Singh R, Bouchareb R, Fish K, Ishikawa K, Lebeche D, Hajjar RJ, Sahoo S. FTO-dependent N(6)-methyladenosine regulates cardiac function during remodeling and repair. Circulation. 2019;139:518–532. doi: 10.1161/CIRCULATIONAHA.118.033794. PubMed DOI PMC
Berulava T, Buchholz E, Elerdashvili V, Pena T, Islam MR, Lbik D, Mohamed BA, Renner A, von Lewinski D, Sacherer M, Bohnsack KE, Bohnsack MT, Jain G, Capece V, Cleve N, Burkhardt S, Hasenfuss G, Fischer A, Toischer K. Changes in m6A RNA methylation contribute to heart failure progression by modulating translation. Eur J Heart Fail. 2020;22:54–66. doi: 10.1002/ejhf.1672. PubMed DOI
Zhang B, Xu Y, Cui X, Jiang H, Luo W, Weng X, Wang Y, Zhao Y, Sun A, Ge J. Alteration of m6A RNA methylation in heart failure with preserved ejection fraction. Front Cardiovasc Med. 2021;8:647806. doi: 10.3389/fcvm.2021.647806. PubMed DOI PMC
Zhang B, Jiang H, Wu J, Cai Y, Dong Z, Zhao Y, Hu Q, Hu K, Sun A, Ge J. m6A demethylase FTO attenuates cardiac dysfunction by regulating glucose uptake and glycolysis in mice with pressure overload-induced heart failure. Signal Transduct Target Ther. 2021;6:377. doi: 10.1038/s41392-021-00699-w. PubMed DOI PMC
Komal S, Gohar A, Althobaiti S, Ahmad Khan I, Cui LG, Zhang LR, Han SN, Shakeel M. ALKBH5 inhibitors as a potential treatment strategy in heart failure-inferences from gene expression profiling. Front Cardiovasc Med. 2023;10:1194311. doi: 10.3389/fcvm.2023.1194311. PubMed DOI PMC
Ju W, Liu K, Ouyang S, Liu Z, He F, Wu J. Changes in N6-methyladenosine modification modulate diabetic cardiomyopathy by reducing myocardial fibrosis and myocyte hypertrophy. Front Cell Dev Biol. 2021;9:702579. doi: 10.3389/fcell.2021.702579. PubMed DOI PMC
Shao Y, Li M, Yu Q, Gong M, Wang Y, Yang X, Liu L, Liu D, Tan Z, Zhang Y, Qu Y, Li H, Wang Y, Jiao L, Zhang Y. CircRNA CDR1as promotes cardiomyocyte apoptosis through activating hippo signaling pathway in diabetic cardiomyopathy. Eur J Pharmacol. 2022;922:174915. doi: 10.1016/j.ejphar.2022.174915. PubMed DOI
Benak D, Benakova S, Plecita-Hlavata L, Hlavackova M. The role of m6A and m6Am RNA modifications in the pathogenesis of diabetes mellitus. Front Endocrinol (Lausanne) 2023;14:1223583. doi: 10.3389/fendo.2023.1223583. PubMed DOI PMC
Zhang B, Jiang H, Dong Z, Sun A, Ge J. The critical roles of m6A modification in metabolic abnormality and cardiovascular diseases. Genes Dis. 2021;8:746–758. doi: 10.1016/j.gendis.2020.07.011. PubMed DOI PMC
Longenecker JZ, Gilbert CJ, Golubeva VA, Martens CR, Accornero F. Epitranscriptomics in the Heart: a Focus on m(6)A. Curr Heart Fail Rep. 2020;17:205–212. doi: 10.1007/s11897-020-00473-z. PubMed DOI PMC
Wu S, Zhang S, Wu X, Zhou X. m(6)A RNA Methylation in Cardiovascular Diseases. Mol Ther. 2020;28:2111–2119. doi: 10.1016/j.ymthe.2020.08.010. PubMed DOI PMC
Qin Y, Li L, Luo E, Hou J, Yan G, Wang D, Qiao Y, Tang C. Role of m6A RNA methylation in cardiovascular disease (Review) Int J Mol Med. 2020;46:1958–1972. doi: 10.3892/ijmm.2020.4746. PubMed DOI PMC
Paramasivam A, Vijayashree Priyadharsini J, Raghunandhakumar S. N6-adenosine methylation (m6A): a promising new molecular target in hypertension and cardiovascular diseases. Hypertens Res. 2020;43:153–154. doi: 10.1038/s41440-019-0338-z. PubMed DOI
Kumari R, Ranjan P, Suleiman ZG, Goswami SK, Li J, Prasad R, Verma SK. mRNA modifications in cardiovascular biology and disease: with a focus on m6A modification. Cardiovasc Res. 2022;118:1680–1692. doi: 10.1093/cvr/cvab160. PubMed DOI PMC
Leptidis S, Papakonstantinou E, Diakou KI, Pierouli K, Mitsis T, Dragoumani K, Bacopoulou F, Sanoudou D, Chrousos GP, Vlachakis D. Epitranscriptomics of cardiovascular diseases (Review) Int J Mol Med. 2022:49. doi: 10.3892/ijmm.2021.5064. PubMed DOI PMC
Chen YS, Ouyang XP, Yu XH, Novák P, Zhou L, He PP, Yin K. N6-Adenosine Methylation (m(6)A) RNA Modification: an Emerging Role in Cardiovascular Diseases. J Cardiovasc Transl Res. 2021;14:857–872. doi: 10.1007/s12265-021-10108-w. PubMed DOI
Zhou W, Wang C, Chang J, Huang Y, Xue Q, Miao C, Wu P. RNA Methylations in Cardiovascular Diseases, Molecular Structure, Biological Functions and Regulatory Roles in Cardiovascular Diseases. Front Pharmacol. 2021;12:722728. doi: 10.3389/fphar.2021.722728. PubMed DOI PMC
Xu Z, Lv B, Qin Y, Zhang B. Emerging Roles and Mechanism of m6A Methylation in Cardiometabolic Diseases. Cells. 2022:11. doi: 10.3390/cells11071101. PubMed DOI PMC
Li Y, Yu H, Zhao W, Xu X, Zhou J, Xu M, Gao W, Yuan G. Analysis of urinary methylated nucleosides of patients with coronary artery disease by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom. 2014;28:2054–2058. https://doi.org/10.1002/rcm.6986, https://doi.org/10.1007/s13361-017-1735-7. PubMed DOI
Ma Y, Liu X, Bi Y, Wang T, Chen C, Wang Y, Han D, Cao F. Alteration of N(6)-Methyladenosine mRNA Methylation in a Human Stem Cell-Derived Cardiomyocyte Model of Tyrosine Kinase Inhibitor-Induced Cardiotoxicity. Front Cardiovasc Med. 2022;9:849175. doi: 10.3389/fcvm.2022.849175. PubMed DOI PMC
Deng W, Jin Q, Li L. Protective mechanism of demethylase fat mass and obesity-associated protein in energy metabolism disorder of hypoxia-reoxygenation-induced cardiomyocytes. Exp Physiol. 2021;106:2423–2433. doi: 10.1113/EP089901. PubMed DOI
Shen W, Li H, Su H, Chen K, Yan J. FTO overexpression inhibits apoptosis of hypoxia/reoxygenation-treated myocardial cells by regulating m6A modification of Mhrt. Mol Cell Biochem. 2021;476:2171–2179. doi: 10.1007/s11010-021-04069-6. PubMed DOI
Ke WL, Huang ZW, Peng CL, Ke YP. m(6)A demethylase FTO regulates the apoptosis and inflammation of cardiomyocytes via YAP1 in ischemia-reperfusion injury. Bioengineered. 2022;13:5443–5452. doi: 10.1080/21655979.2022.2030572. PubMed DOI PMC
Zhang X, Fu Q, Xu L, Yang Y, Zhao W, Zhang Y, Li H, Mi W. Dexmedetomidine Postconditioning Alleviates Hypoxia/Reoxygenation Injury in Senescent Myocardial Cells by Regulating lncRNA H19 and m(6)A Modification. Oxidative Medicine and Cellular Longevity. 2020;2020:9250512. doi: 10.1155/2020/9250512. PubMed DOI PMC
Cui Y, Wang P, Li M, Wang Y, Tang X, Cui J, Chen Y, Zhang T. Cinnamic acid mitigates left ventricular hypertrophy and heart failure in part through modulating FTO-dependent N(6)-methyladenosine RNA modification in cardiomyocytes. Biomed Pharmacother. 2023;165:115168. doi: 10.1016/j.biopha.2023.115168. PubMed DOI
Yu P, Wang J, Xu GE, Zhao X, Cui X, Feng J, Sun J, Wang T, Spanos M, Lehmann HI, Li G, Xu J, Wang L, Xiao J. RNA m(6)A-Regulated circ-ZNF609 Suppression Ameliorates Doxorubicin-Induced Cardiotoxicity by Upregulating FTO. JACC Basic Transl Sci. 2023;8:677–698. doi: 10.1016/j.jacbts.2022.12.005. PubMed DOI PMC
Benak D, Holzerova K, Hrdlicka J, Kolar F, Olsen M, Karelson M, Hlavackova M. Epitranscriptomic regulation in fasting hearts: implications for cardiac health. RNA Biol. 2024;21:1–14. doi: 10.1080/15476286.2024.2307732. PubMed DOI PMC
Gong R, Wang X, Li H, Liu S, Jiang Z, Zhao Y, Yu Y, Han Z, Yu Y, Dong C, Li S, Xu B, Zhang W, Wang N, Li X, Gao X, Yang F, Bamba D, Ma W, Liu Y, Cai B. Loss of m(6)A methyltransferase METTL3 promotes heart regeneration and repair after myocardial injury. Pharmacol Res. 2021;174:105845. doi: 10.1016/j.phrs.2021.105845. PubMed DOI
Wu C, Chen Y, Wang Y, Xu C, Cai Y, Zhang R, Peng F, Wang S. The m(6)A methylation enzyme METTL14 regulates myocardial ischemia/reperfusion injury through the Akt/mTOR signaling pathway. Mol Cell Biochem. 2023 doi: 10.1007/s11010-023-04808-x. PubMed DOI
Benak D, Kolar F, Zhang L, Devaux Y, Hlavackova M. RNA modification m(6)Am: the role in cardiac biology. Epigenetics. 2023;18:2218771. doi: 10.1080/15592294.2023.2218771. PubMed DOI PMC
Wei C, Gershowitz A, Moss B. N6, O2’-dimethyladenosine a novel methylated ribonucleoside next to the 5’ terminal of animal cell and virus mRNAs. Nature. 1975;257:251–253. doi: 10.1038/257251a0. PubMed DOI
Bokar JA. The biosynthesis and functional roles of methylated nucleosides in eukaryotic mRNA. In: Grosjean H, editor. Fine-Tuning of RNA Functions by Modification and Editing. Berlin, Heidelberg: Springer Berlin Heidelberg; 2005. pp. 141–177. DOI
Akichika S, Hirano S, Shichino Y, Suzuki T, Nishimasu H, Ishitani R, Sugita A, Hirose Y, Iwasaki S, Nureki O, Suzuki T. Cap-specific terminal N (6)-methylation of RNA by an RNA polymerase II-associated methyltransferase. Science. 2019:363. doi: 10.1126/science.aav0080. PubMed DOI
Sun H, Zhang M, Li K, Bai D, Yi C. Cap-specific, terminal N(6)-methylation by a mammalian m(6)Am methyltransferase. Cell Res. 2019;29:80–82. doi: 10.1038/s41422-018-0117-4. PubMed DOI PMC
Chen H, Gu L, Orellana EA, Wang Y, Guo J, Liu Q, Wang L, Shen Z, Wu H, Gregory RI, Xing Y, Shi Y. METTL4 is an snRNA m(6)Am methyltransferase that regulates RNA splicing. Cell Res. 2020;30:544–547. doi: 10.1038/s41422-019-0270-4. PubMed DOI PMC
Goh YT, Koh CWQ, Sim DY, Roca X, Goh WSS. METTL4 catalyzes m6Am methylation in U2 snRNA to regulate pre-mRNA splicing. Nucleic Acids Res. 2020;48:9250–9261. doi: 10.1093/nar/gkaa684. PubMed DOI PMC
Mauer J, Luo X, Blanjoie A, Jiao X, Grozhik AV, Patil DP, Linder B, Pickering BF, Vasseur JJ, Chen Q, Gross SS, Elemento O, Debart F, Kiledjian M, Jaffrey SR. Reversible methylation of m(6)A(m) in the 5’ cap controls mRNA stability. Nature. 2017;541:371–375. doi: 10.1038/nature21022. PubMed DOI PMC
Mauer J, Jaffrey SR. FTO, m(6) A(m), and the hypothesis of reversible epitranscriptomic mRNA modifications. FEBS Lett. 2018;592:2012–2022. doi: 10.1002/1873-3468.13092. PubMed DOI
Mauer J, Sindelar M, Despic V, Guez T, Hawley BR, Vasseur JJ, Rentmeister A, Gross SS, Pellizzoni L, Debart F, Goodarzi H, Jaffrey SR. FTO controls reversible m(6)Am RNA methylation during snRNA biogenesis. Nat Chem Biol. 2019;15:340–347. doi: 10.1038/s41589-019-0231-8. PubMed DOI PMC
Dunn DB. The occurrence of 1-methyladenine in ribonucleic acid. Biochim Biophys Acta. 1961;46:198–200. doi: 10.1016/0006-3002(61)90668-0. PubMed DOI
Helm M, Giegé R, Florentz C. A Watson-Crick base-pair-disrupting methyl group (m1A9) is sufficient for cloverleaf folding of human mitochondrial tRNALys. Biochemistry. 1999;38:13338–13346. doi: 10.1021/bi991061g. PubMed DOI
Sharma S, Watzinger P, Kötter P, Entian KD. Identification of a novel methyltransferase, Bmt2, responsible for the N-1-methyl-adenosine base modification of 25S rRNA in Saccharomyces cerevisiae. Nucleic Acids Res. 2013;41:5428–5443. doi: 10.1093/nar/gkt195. PubMed DOI PMC
Dominissini D, Nachtergaele S, Moshitch-Moshkovitz S, Peer E, Kol N, Ben-Haim MS, Dai Q, Di Segni A, Salmon-Divon M, Clark WC, Zheng G, Pan T, Solomon O, Eyal E, Hershkovitz V, Han D, Doré LC, Amariglio N, Rechavi G, He C. The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA. Nature. 2016;530:441–446. doi: 10.1038/nature16998. PubMed DOI PMC
Safra M, Sas-Chen A, Nir R, Winkler R, Nachshon A, Bar-Yaacov D, Erlacher M, Rossmanith W, Stern-Ginossar N, Schwartz S. The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution. Nature. 2017;551:251–255. doi: 10.1038/nature24456. PubMed DOI
Li X, Xiong X, Zhang M, Wang K, Chen Y, Zhou J, Mao Y, Lv J, Yi D, Chen XW, Wang C, Qian SB, Yi C. Base-Resolution Mapping Reveals Distinct m(1)A Methylome in Nuclear- and Mitochondrial-Encoded Transcripts. Mol Cell. 2017;68:993–1005.e1009. doi: 10.1016/j.molcel.2017.10.019. PubMed DOI PMC
Chujo T, Suzuki T. Trmt61B is a methyltransferase responsible for 1-methyladenosine at position 58 of human mitochondrial tRNAs. Rna. 2012;18:2269–2276. doi: 10.1261/rna.035600.112. PubMed DOI PMC
Bar-Yaacov D, Frumkin I, Yashiro Y, Chujo T, Ishigami Y, Chemla Y, Blumberg A, Schlesinger O, Bieri P, Greber B, Ban N, Zarivach R, Alfonta L, Pilpel Y, Suzuki T, Mishmar D. Mitochondrial 16S rRNA Is Methylated by tRNA Methyltransferase TRMT61B in All Vertebrates. PLoS Biol. 2016;14:e1002557. doi: 10.1371/journal.pbio.1002557. PubMed DOI PMC
Waku T, Nakajima Y, Yokoyama W, Nomura N, Kako K, Kobayashi A, Shimizu T, Fukamizu A. NML-mediated rRNA base methylation links ribosomal subunit formation to cell proliferation in a p53-dependent manner. J Cell Sci. 2016;129:2382–2393. doi: 10.1242/jcs.183723. PubMed DOI
Liu F, Clark W, Luo G, Wang X, Fu Y, Wei J, Wang X, Hao Z, Dai Q, Zheng G, Ma H, Han D, Evans M, Klungland A, Pan T, He C. ALKBH1-mediated tRNA demethylation regulates translation. Cell. 2016;167:816–828.e816. doi: 10.1016/j.cell.2016.09.038. PubMed DOI PMC
Li X, Xiong X, Wang K, Wang L, Shu X, Ma S, Yi C. Transcriptome-wide mapping reveals reversible and dynamic N(1)-methyladenosine methylome. Nat Chem Biol. 2016;12:311–316. doi: 10.1038/nchembio.2040. PubMed DOI
Chen Z, Qi M, Shen B, Luo G, Wu Y, Li J, Lu Z, Zheng Z, Dai Q, Wang H. Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs. Nucleic Acids Res. 2019;47:2533–2545. doi: 10.1093/nar/gky1250. PubMed DOI PMC
Oerum S, Dégut C, Barraud P, Tisné C. m1A Post-Transcriptional Modification in tRNAs. Biomolecules. 2017:7. doi: 10.3390/biom7010020. PubMed DOI PMC
Shima H, Igarashi K. N 1-methyladenosine (m1A) RNA modification: the key to ribosome control. J Biochem. 2020;167:535–539. doi: 10.1093/jb/mvaa026. PubMed DOI
Zhao BS, Roundtree IA, He C. Post-transcriptional gene regulation by mRNA modifications. Nat Rev Mol Cell Biol. 2017;18:31–42. doi: 10.1038/nrm.2016.132. PubMed DOI PMC
Wu Y, Zhan S, Xu Y, Gao X. RNA modifications in cardiovascular diseases, the potential therapeutic targets. Life Sci. 2021;278:119565. doi: 10.1016/j.lfs.2021.119565. PubMed DOI
Cohn WE. Some results of the applications of ion-exchange chromatography to nucleic acid chemistry. J Cell Physiol Suppl. 1951;38:21–40. doi: 10.1002/jcp.1030380405. PubMed DOI
Xue C, Chu Q, Zheng Q, Jiang S, Bao Z, Su Y, Lu J, Li L. Role of main RNA modifications in cancer: N(6)-methyladenosine, 5-methylcytosine, and pseudouridine. Signal Transduct Target Ther. 2022;7:142. doi: 10.1038/s41392-022-01003-0. PubMed DOI PMC
Sun H, Li K, Liu C, Yi C. Regulation and functions of non-m(6)A mRNA modifications. Nat Rev Mol Cell Biol. 2023 doi: 10.1038/s41580-023-00622-x. PubMed DOI
Rintala-Dempsey AC, Kothe U. Eukaryotic stand-alone pseudouridine synthases - RNA modifying enzymes and emerging regulators of gene expression? RNA Biol. 2017;14:1185–1196. doi: 10.1080/15476286.2016.1276150. PubMed DOI PMC
Li X, Ma S, Yi C. Pseudouridine: the fifth RNA nucleotide with renewed interests. Curr Opin Chem Biol. 2016;33:108–116. doi: 10.1016/j.cbpa.2016.06.014. PubMed DOI
Zhao BS, He C. Pseudouridine in a new era of RNA modifications. Cell Res. 2015;25:153–154. doi: 10.1038/cr.2014.143. PubMed DOI PMC
Wu G, Adachi H, Ge J, Stephenson D, Query CC, Yu YT. Pseudouridines in U2 snRNA stimulate the ATPase activity of Prp5 during spliceosome assembly. Embo j. 2016;35:654–667. doi: 10.15252/embj.201593113. PubMed DOI PMC
Levi O, Arava YS. Pseudouridine-mediated translation control of mRNA by methionine aminoacyl tRNA synthetase. Nucleic Acids Res. 2021;49:432–443. doi: 10.1093/nar/gkaa1178. PubMed DOI PMC
Borchardt EK, Martinez NM, Gilbert WV. Regulation and Function of RNA Pseudouridylation in Human Cells. Annu Rev Genet. 2020;54:309–336. doi: 10.1146/annurev-genet-112618-043830. PubMed DOI PMC
Jalan A, Jayasree PJ, Karemore P, Narayan KP, Khandelia P. Decoding the ‘Fifth’ Nucleotide: Impact of RNA Pseudouridylation on Gene Expression and Human Disease. Mol Biotechnol. 2023 doi: 10.1007/s12033-023-00792-1. PubMed DOI
Razavi AC, Bazzano LA, He J, Li S, Fernandez C, Whelton SP, Krousel-Wood M, Nierenberg JL, Shi M, Li C, Mi X, Kinchen J, Kelly TN. Pseudouridine and N-formylmethionine associate with left ventricular mass index: Metabolome-wide association analysis of cardiac remodeling. J Mol Cell Cardiol. 2020;140:22–29. doi: 10.1016/j.yjmcc.2020.02.005. PubMed DOI PMC
Alexander D, Lombardi R, Rodriguez G, Mitchell MM, Marian AJ. Metabolomic distinction and insights into the pathogenesis of human primary dilated cardiomyopathy. Eur J Clin Invest. 2011;41:527–538. doi: 10.1111/j.1365-2362.2010.02441.x. PubMed DOI PMC
Dunn WB, Broadhurst DI, Deepak SM, Buch MH, McDowell G, Spasic I, Ellis DI, Brooks N, Kell DB, Neyses L. Serum metabolomics reveals many novel metabolic markers of heart failure, including pseudouridine and 2-oxoglutarate. Metabolomics. 2007;3:413–426. doi: 10.1007/s11306-007-0063-5. DOI
Nagasawa CK, Kibiryeva N, Marshall J, O’Brien JE, Bittel DC. scaRNA1 levels alter pseudouridylation in spliceosomal RNA U2 affecting alternative mRNA splicing and embryonic development. Pediatric Cardiology. 2020;41:341–349. doi: 10.1007/s00246-019-02263-4. PubMed DOI
Patil P, Kibiryeva N, Uechi T, Marshall J, O’Brien JE, Jr, Artman M, Kenmochi N, Bittel DC. scaRNAs regulate splicing and vertebrate heart development. Biochim Biophys Acta. 2015;1852:1619–1629. doi: 10.1016/j.bbadis.2015.04.016. PubMed DOI
Bohnsack KE, Höbartner C, Bohnsack MT. Eukaryotic 5-methylcytosine (m5C) RNA methyltransferases: mechanisms, cellular functions, and links to disease. Genes (Basel) 2019:10. doi: 10.3390/genes10020102. PubMed DOI PMC
Wang YY, Tian Y, Li YZ, Liu YF, Zhao YY, Chen LH, Zhang C. The role of m5C methyltransferases in cardiovascular diseases. Front Cardiovasc Med. 2023;10:1225014. doi: 10.3389/fcvm.2023.1225014. PubMed DOI PMC
Haag S, Sloan KE, Ranjan N, Warda AS, Kretschmer J, Blessing C, Hübner B, Seikowski J, Dennerlein S, Rehling P, Rodnina MV, Höbartner C, Bohnsack MT. NSUN3 and ABH1 modify the wobble position of mt-tRNAMet to expand codon recognition in mitochondrial translation. Embo j. 2016;35:2104–2119. doi: 10.15252/embj.201694885. PubMed DOI PMC
Fu L, Guerrero CR, Zhong N, Amato NJ, Liu Y, Liu S, Cai Q, Ji D, Jin SG, Niedernhofer LJ, Pfeifer GP, Xu GL, Wang Y. Tet-mediated formation of 5-hydroxymethylcytosine in RNA. J Am Chem Soc. 2014;136:11582–11585. doi: 10.1021/ja505305z. PubMed DOI PMC
Yang X, Yang Y, Sun BF, Chen YS, Xu JW, Lai WY, Li A, Wang X, Bhattarai DP, Xiao W, Sun HY, Zhu Q, Ma HL, Adhikari S, Sun M, Hao YJ, Zhang B, Huang CM, Huang N, Jiang GB, Zhao YL, Wang HL, Sun YP, Yang YG. 5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and ALYREF as an m(5)C reader. Cell Res. 2017;27:606–625. doi: 10.1038/cr.2017.55. PubMed DOI PMC
Chen X, Li A, Sun BF, Yang Y, Han YN, Yuan X, Chen RX, Wei WS, Liu Y, Gao CC, Chen YS, Zhang M, Ma XD, Liu ZW, Luo JH, Lyu C, Wang HL, Ma J, Zhao YL, Zhou FJ, Huang Y, Xie D, Yang YG. 5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs. Nat Cell Biol. 2019;21:978–990. doi: 10.1038/s41556-019-0361-y. PubMed DOI
Squires JE, Preiss T. Function and detection of 5-methylcytosine in eukaryotic RNA. Epigenomics. 2010;2:709–715. doi: 10.2217/epi.10.47. PubMed DOI
Chen YS, Yang WL, Zhao YL, Yang YG. Dynamic transcriptomic m(5) C and its regulatory role in RNA processing. Wiley Interdiscip Rev RNA. 2021;12:e1639. doi: 10.1002/wrna.1639. PubMed DOI
Huang T, Chen W, Liu J, Gu N, Zhang R. Genome-wide identification of mRNA 5-methylcytosine in mammals. Nature Structural & Molecular Biology. 2019;26:380–388. doi: 10.1038/s41594-019-0218-x. PubMed DOI
Metodiev MD, Spåhr H, Loguercio Polosa P, Meharg C, Becker C, Altmueller J, Habermann B, Larsson NG, Ruzzenente B. NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly. PLoS Genet. 2014;10:e1004110. doi: 10.1371/journal.pgen.1004110. PubMed DOI PMC
Ghanbarian H, Wagner N, Polo B, Baudouy D, Kiani J, Michiels JF, Cuzin F, Rassoulzadegan M, Wagner KD. Dnmt2/Trdmt1 as mediator of RNA polymerase II transcriptional activity in cardiac growth. PLoS One. 2016;11:e0156953. doi: 10.1371/journal.pone.0156953. PubMed DOI PMC
Varma E, Burghaus J, Schwarzl T, Sekaran T, Gupta P, Górska AA, Hofmann C, Stroh C, Jürgensen L, Kamuf-Schenk V, Li X, Medert R, Leuschner F, Kmietczyk V, Freichel M, Katus HA, Hentze MW, Frey N, Völkers M. Translational control of Ybx1 expression regulates cardiac function in response to pressure overload in vivo. Basic Res Cardiol. 2023;118:25. doi: 10.1007/s00395-023-00996-1. PubMed DOI PMC
Yang R, Li L, Hou Y, Li Y, Zhang J, Yang N, Zhang Y, Ji W, Yu T, Lv L, Liang H, Li X, Li T, Shan H. Long non-coding RNA KCND1 protects hearts from hypertrophy by targeting YBX1. Cell Death Dis. 2023;14:344. doi: 10.1038/s41419-023-05852-7. PubMed DOI PMC
Wang Y, Zan Y, Huang Y, Peng X, Ma S, Ren J, Li X, Wei L, Wang X, Yuan Y, Tang J, Zhan Z, Wang Z, Ding Y. NSUN2 alleviates doxorubicin-induced myocardial injury through Nrf2-mediated antioxidant stress. Cell Death Discov. 2023;9:43. doi: 10.1038/s41420-022-01294-w. PubMed DOI PMC
Brennicke A, Marchfelder A, Binder S. RNA editing. FEMS Microbiol Rev. 1999;23:297–316. doi: 10.1111/j.1574-6976.1999.tb00401.x. PubMed DOI
Gott JM, Emeson RB. Functions and mechanisms of RNA editing. Annu Rev Genet. 2000;34:499–531. doi: 10.1146/annurev.genet.34.1.499. PubMed DOI
Ganem NS, Lamm AT. A-to-I RNA editing - thinking beyond the single nucleotide. RNA Biol. 2017;14:1690–1694. doi: 10.1080/15476286.2017.1364830. PubMed DOI PMC
Dominissini D, Moshitch-Moshkovitz S, Amariglio N, Rechavi G. Adenosine-to-inosine RNA editing meets cancer. Carcinogenesis. 2011;32:1569–1577. doi: 10.1093/carcin/bgr124. PubMed DOI
Bhakta S, Tsukahara T. C-to-U RNA Editing: A Site Directed RNA Editing Tool for Restoration of Genetic Code. Genes (Basel) 2022:13. doi: 10.3390/genes13091636. PubMed DOI PMC
Sowden MP, Ballatori N, Jensen KL, Reed LH, Smith HC. The editosome for cytidine to uridine mRNA editing has a native complexity of 27S: identification of intracellular domains containing active and inactive editing factors. J Cell Sci. 2002;115:1027–1039. doi: 10.1242/jcs.115.5.1027. PubMed DOI
Nishikura K. A-to-I editing of coding and non-coding RNAs by ADARs. Nat Rev Mol Cell Biol. 2016;17:83–96. doi: 10.1038/nrm.2015.4. PubMed DOI PMC
Moore JBt, Sadri G, Fischer AG, Weirick T, Militello G, Wysoczynski M, Gumpert AM, Braun T, Uchida S. The A-to-I RNA editing enzyme adar1 is essential for normal embryonic cardiac growth and development. Circ Res. 2020;127:550–552. doi: 10.1161/CIRCRESAHA.120.316932. PubMed DOI PMC
El Azzouzi H, Vilaça AP, Feyen DAM, Gommans WM, de Weger RA, Doevendans PAF, Sluijter JPG. Cardiomyocyte Specific Deletion of ADAR1 Causes Severe Cardiac Dysfunction and Increased Lethality. Front Cardiovasc Med. 2020;7:30. doi: 10.3389/fcvm.2020.00030. PubMed DOI PMC
Garcia-Gonzalez C, Dieterich C, Maroli G, Wiesnet M, Wietelmann A, Li X, Yuan X, Graumann J, Stellos K, Kubin T, Schneider A, Braun T. ADAR1 prevents autoinflammatory processes in the heart mediated by IRF7. Circ Res. 2022;131:580–597. doi: 10.1161/CIRCRESAHA.122.320839. PubMed DOI
Borik S, Simon AJ, Nevo-Caspi Y, Mishali D, Amariglio N, Rechavi G, Paret G. Increased RNA editing in children with cyanotic congenital heart disease. Intensive Care Med. 2011;37:1664–1671. doi: 10.1007/s00134-011-2296-z. PubMed DOI
Kokot KE, Kneuer JM, John D, Rebs S, Möbius-Winkler MN, Erbe S, Müller M, Andritschke M, Gaul S, Sheikh BN, Haas J, Thiele H, Müller OJ, Hille S, Leuschner F, Dimmeler S, Streckfuss-Bömeke K, Meder B, Laufs U, Boeckel JN. Reduction of A-to-I RNA editing in the failing human heart regulates formation of circular RNAs. Basic Res Cardiol. 2022;117:32. doi: 10.1007/s00395-022-00940-9. PubMed DOI PMC
Altaf F, Vesely C, Sheikh AM, Munir R, Shah STA, Tariq A. Modulation of ADAR mRNA expression in patients with congenital heart defects. PLoS One. 2019;14:e0200968. doi: 10.1371/journal.pone.0200968. PubMed DOI PMC
Wu X, Wang L, Wang K, Li J, Chen R, Wu X, Ni G, Liu C, Das S, Sluijter JPG, Li X, Xiao J. ADAR2 increases in exercised heart and protects against myocardial infarction and doxorubicin-induced cardiotoxicity. Mol Ther. 2022;30:400–414. doi: 10.1016/j.ymthe.2021.07.004. PubMed DOI PMC
Birgaoanu M, Sachse M, Gatsiou A. RNA editing therapeutics: advances, challenges and perspectives on combating heart disease. Cardiovasc Drugs Ther. 2023;37:401–411. doi: 10.1007/s10557-022-07391-3. PubMed DOI PMC