N6-methyladenosine modifications: interactions with novel RNA-binding proteins and roles in signal transduction

References

• Potapov V, Fu X, Dai N, et al. Base modifications affecting RNA polymerase and reverse transcriptase fidelity. Nucleic Acids Res. 2018;46:5753–5763.
   PubMed Web of Science ®Google Scholar
• Jaffrey SR, Kharas MG. Emerging links between m(6)A and misregulated mRNA methylation in cancer. Genome Med. 2017;9:2.
   PubMed Web of Science ®Google Scholar
• Wang S, Chai P, Jia R, et al. Novel insights on m(6)A RNA methylation in tumorigenesis: a double-edged sword. Mol Cancer. 2018;17:101.
   PubMed Web of Science ®Google Scholar
• Wang Y, Li Y, Yue M, et al. N(6)-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications. Nat Neurosci. 2018;21:195–206.
   PubMed Web of Science ®Google Scholar
• Wang CX, Cui GS, Liu X, et al. METTL3-mediated m6A modification is required for cerebellar development. PLoS Biol. 2018;16:e2004880.
   PubMed Web of Science ®Google Scholar
• Tang C, Klukovich R, Peng H, et al. ALKBH5-dependent m6A demethylation controls splicing and stability of long 3’-UTR mRNAs in male germ cells. Proc Natl Acad Sci USA. 2018;115:E325–e33.
   PubMed Web of Science ®Google Scholar
• Kasowitz SD, Ma J, Anderson SJ, et al. Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development. PLoS Genet. 2018;14:e1007412.
   PubMed Web of Science ®Google Scholar
• Huang X, Broxmeyer HE. m(6)A reader suppression bolsters HSC expansion. Cell Res. 2018;28:875–876.
   PubMed Web of Science ®Google Scholar
• Xiang Y, Laurent B, Hsu CH, et al. RNA m(6)A methylation regulates the ultraviolet-induced DNA damage response. Nature. 2017;543:573–576.
   PubMed Web of Science ®Google Scholar
• Wojtas MN, Pandey RR, Mendel M, et al. Regulation of m(6)A transcripts by the 3’–>5’ RNA helicase YTHDC2 is essential for a successful meiotic program in the mammalian germline. Mol Cell. 2017;68(374–87):e12.
   Google Scholar
• Kruttner S, Caroni P. m(6)A-epitranscriptome modulates memory strength. Cell Res. 2019;29:4–5.
   PubMed Web of Science ®Google Scholar
• Zhong X, Yu J, Frazier K, et al. Circadian clock regulation of hepatic lipid metabolism by modulation of m(6)A mRNA methylation. Cell Rep. 2018;25(1816–28):e4.
   Google Scholar
• Shi H, Zhang X, Weng YL, et al. m(6)A facilitates hippocampus-dependent learning and memory through YTHDF1. Nature. 2018;563:249–253.
   PubMed Web of Science ®Google Scholar
• Fustin JM, Kojima R, Itoh K, et al. Two Ck1δ transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock. Proc Natl Acad Sci USA. 2018;115:5980–5985.
   PubMed Web of Science ®Google Scholar
• Yang Y, Hsu PJ, Chen YS, et al. Dynamic transcriptomic m(6)A decoration: writers, erasers, readers and functions in RNA metabolism. Cell Res. 2018;28:616–624.
   PubMed Web of Science ®Google Scholar
• Wen J, Lv R, Ma H, et al. Zc3h13 regulates nuclear RNA m(6)A methylation and mouse embryonic stem cell self-renewal. Mol Cell. 2018;69(1028–1038):e6.
   Google Scholar
• Knuckles P, Lence T, Haussmann IU, et al. Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the <ins style="background: springGreen">m 6 A machinery component Wtap/Fl(2)d. Genes Dev. 2018;32:415–429.
   PubMed Web of Science ®Google Scholar
• Warda AS, Kretschmer J, Hackert P, et al. Human METTL16 is a N(6)-methyladenosine (m(6)A) methyltransferase that targets pre-mRNAs and various non-coding RNAs. EMBO Rep. 2017;18:2004–2014.
   PubMed Web of Science ®Google Scholar
• Pendleton KE, Chen B, Liu K, et al. The U6 snRNA m(6)A methyltransferase METTL16 regulates SAM synthetase intron retention. Cell. 2017;169(824–835):e14.
   Google Scholar
• Ruzicka K, Zhang M, Campilho A, et al. Identification of factors required for <ins style="background: springGreen">m 6 A mRNA methylation in Arabidopsis reveals a role for the conserved E3 ubiquitin ligase HAKAI. New Phytol. 2017;215:157–172.
   PubMed Web of Science ®Google Scholar
• Wu Y, Zhou C, Yuan Q. Role of DNA and RNA N6-adenine methylation in regulating stem cell fate. Curr Stem Cell Res Ther. 2018;13:31–38.
   PubMed Web of Science ®Google Scholar
• Wang S, Sun C, Li J, et al. Roles of RNA methylation by means of N(6)-methyladenosine (m(6)A) in human cancers. Cancer Lett. 2017;408:112–120.
   PubMed Web of Science ®Google Scholar
• Liao S, Sun H, Xu C. YTH Domain: A Family of N(6)-methyladenosine (m(6)A) Readers. Genomics Proteomics Bioinf. 2018;16:99–107.
   PubMed Web of Science ®Google Scholar
• Patil DP, Pickering BF, Jaffrey SR. Reading m(6)A in the Transcriptome: m(6)A-binding proteins. Trends Cell Biol. 2018;28:113–127.
   PubMed Web of Science ®Google Scholar
• Liu N, Zhou KI, Parisien M, et al. N6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein. Nucleic Acids Res. 2017;45:6051–6063.
   PubMed Web of Science ®Google Scholar
• Liu N, Dai Q, Zheng G, et al. N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature. 2015;518:560–564.
   PubMed Web of Science ®Google Scholar
• Alarcon CR, Goodarzi H, Lee H, et al. HNRNPA2B1 Is a Mediator of m(6)A-Dependent Nuclear RNA Processing Events. Cell.. 2015;162:1299–1308.
   PubMed Web of Science ®Google Scholar
• Wu B, Su S, Patil DP, et al. Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1. Nat Commun. 2018;9:420.
   PubMed Web of Science ®Google Scholar
• Jackson RJ, Hellen CU, Pestova TV. The mechanism of eukaryotic translation initiation and principles of its regulation. Nat Rev Mol Cell Biol. 2010;11:113–127.
   PubMed Web of Science ®Google Scholar
• Marintchev A, Edmonds KA, Marintcheva B, et al. Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation. Cell. 2009;136:447–460.
   PubMed Web of Science ®Google Scholar
• Lee AS, Kranzusch PJ, Doudna JA, et al. eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation. Nature. 2016;536:96–99.
   PubMed Web of Science ®Google Scholar
• de la Parra C, Ernlund A, Alard A, et al. A widespread alternate form of cap-dependent mRNA translation initiation. Nat Commun. 2018;9:3068.
   PubMed Web of Science ®Google Scholar
• Meyer KD, Patil DP, Zhou J, et al. 5’ UTR m(6)A promotes cap-independent translation. Cell. 2015;163:999–1010.
   PubMed Web of Science ®Google Scholar
• Coots RA, Liu XM, Mao Y, et al. m(6)A facilitates eIF4F-Independent mRNA translation. Mol Cell. 2017;68(504–514):e7.
   Google Scholar
• Zhou J, Wan J, Gao X, et al. Dynamic m(6)A mRNA methylation directs translational control of heat shock response. Nature. 2015;526:591–594.
   PubMed Web of Science ®Google Scholar
• Akichika S, Hirano S, Shichino Y, et al. Cap-specific terminal N <ins style="background: springGreen">6-methylation of RNA by an RNA polymerase II–associated methyltransferase. Science. 2019;363.
   PubMedGoogle Scholar
• Wang X, Zhao BS, Roundtree IA, et al. N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell. 2015;161:1388–1399.
   PubMed Web of Science ®Google Scholar
• Choe J, Lin S, Zhang W, et al. mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis. Nature. 2018;561:556–560.
   PubMed Web of Science ®Google Scholar
• Huang H, Weng H, Sun W, et al. Recognition of RNA N(6)-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol. 2018;20:285–295.
   PubMed Web of Science ®Google Scholar
• Weng H, Huang H, Wu H, et al. METTL14 inhibits hematopoietic stem/progenitor differentiation and promotes leukemogenesis via mRNA m(6)A modification. Cell Stem Cell. 2018;22:191–205,e9.
   PubMed Web of Science ®Google Scholar
• Vu LP, Pickering BF, Cheng Y, et al. The N(6)-methyladenosine (m(6)A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nat Med. 2017;23:1369–1376.
   PubMed Web of Science ®Google Scholar
• Huang X, Zhang H, Guo X, et al. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in cancer. J Hematol Oncol. 2018;11:88.
   PubMed Web of Science ®Google Scholar
• Busch B, Bley N, Muller S, et al. The oncogenic triangle of HMGA2, LIN28B and IGF2BP1 antagonizes tumor-suppressive actions of the let-7 family. Nucleic Acids Res. 2016;44:3845–3864.
   PubMed Web of Science ®Google Scholar
• Muller S, Bley N, Glass M, et al. IGF2BP1 enhances an aggressive tumor cell phenotype by impairing miRNA-directed downregulation of oncogenic factors. Nucleic Acids Res. 2018;46:6285–6303.
   PubMed Web of Science ®Google Scholar
• Müller S, Glaß M, Singh AK, et al. IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner. Nucleic Acids Res. 2019;47:375–390.
   PubMed Web of Science ®Google Scholar
• Wu R, Li A, Sun B, et al. A novel m(6)A reader Prrc2a controls oligodendroglial specification and myelination. Cell Res. 2019;29:23–41.
   PubMed Web of Science ®Google Scholar
• Arguello AE, DeLiberto AN, Kleiner RE. RNA chemical proteomics reveals the N(6)-methyladenosine (m(6)A)-regulated protein-RNA interactome. J Am Chem Soc. 2017;139:17249–17252.
   PubMed Web of Science ®Google Scholar
• Zhang F, Kang Y, Wang M, et al. Fragile X mental retardation protein modulates the stability of its m6A-marked messenger RNA targets. Hum Mol Genet. 2018;27:3936–3950.
   PubMed Web of Science ®Google Scholar
• Edupuganti RR, Geiger S, Lindeboom RGH, et al. N(6)-methyladenosine (m(6)A) recruits and repels proteins to regulate mRNA homeostasis. Nat Struct Mol Biol. 2017;24:870–878.
   PubMed Web of Science ®Google Scholar
• Lebedeva S, Jens M, Theil K, et al. Transcriptome-wide analysis of regulatory interactions of the RNA-binding protein HuR. Mol Cell. 2011;43:340–352.
   PubMed Web of Science ®Google Scholar
• Dominissini D, Moshitch-Moshkovitz S, Schwartz S, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 2012;485:201–206.
   PubMed Web of Science ®Google Scholar
• Geula S, Moshitch-Moshkovitz S, Dominissini D, et al. ins style="background: springGreen">m 6 A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science. 2015;347::1002–1006.
   PubMed Web of Science ®Google Scholar
• Wang Y, Li Y, Toth JI, et al. N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat Cell Biol. 2014;16:191–198.
   PubMed Web of Science ®Google Scholar
• Batista PJ, Molinie B, Wang J, et al. m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell. 2014;15:707–719.
   PubMed Web of Science ®Google Scholar
• Meisner NC, Filipowicz W. Properties of the regulatory RNA-binding protein HuR and its role in controlling miRNA repression. Adv Exp Med Biol. 2011;700:106–123.
   PubMed Web of Science ®Google Scholar
• Li L, Zang L, Zhang F, et al. Fat mass and obesity-associated (FTO) protein regulates adult neurogenesis. Hum Mol Genet. 2017;26:2398–2411.
   PubMed Web of Science ®Google Scholar
• Visvanathan A, Patil V, Arora A, et al. Essential role of METTL3-mediated m(6)A modification in glioma stem-like cells maintenance and radioresistance. Oncogene. 2018;37:522–533.
   PubMed Web of Science ®Google Scholar
• Chen K, Lu Z, Wang X, et al. High-resolution <ins style="background: springGreen">N 6 -Methyladenosine (<ins style="background: springGreen">m 6 A) map using photo-crosslinking-assisted <ins style="background: springGreen">m 6 A Sequencing. Angew Chem Int Ed Engl. 2015;54:1587–1590.
   PubMed Web of Science ®Google Scholar
• Slobodin B, Han R, Calderone V, et al. Transcription impacts the efficiency of mRNA translation via co-transcriptional N6-adenosine methylation. Cell. 2017;169:326–337,e12.
   PubMed Web of Science ®Google Scholar
• Kretschmer J, Rao H, Hackert P, et al. The <ins style="background: springGreen">m 6 A reader protein YTHDC2 interacts with the small ribosomal subunit and the 5′–3′ exoribonuclease XRN1. Rna. 2018;24:1339–1350.
   PubMed Web of Science ®Google Scholar
• Shah A, Rashid F, Awan HM, et al. The DEAD-Box RNA Helicase DDX3 Interacts with <ins style="background: springGreen">m 6 A RNA Demethylase ALKBH5. Stem Cells Int. 2017;2017:8596135.
   PubMed Web of Science ®Google Scholar
• Zheng Q, Hou J, Zhou Y, et al. The RNA helicase DDX46 inhibits innate immunity by entrapping m(6)A-demethylated antiviral transcripts in the nucleus. Nat Immunol. 2017;18:1094–1103.
   PubMed Web of Science ®Google Scholar
• Hao H, Hao S, Chen H, et al. N6-methyladenosine modification and METTL3 modulate enterovirus 71 replication. Nucleic Acids Res. 2019;47:362–374.
   PubMed Web of Science ®Google Scholar
• Liu Y, Zheng Z, Shu B, et al. SUMO modification stabilizes enterovirus 71 polymerase 3D to facilitate viral replication. J Virol. 2016;90:10472–10485.
   PubMed Web of Science ®Google Scholar
• Imanishi M, Tsuji S, Suda A, et al. Detection of N(6)-methyladenosine based on the methyl-sensitivity of MazF RNA endonuclease. Chem Commun. 2017;53:12930–12933.
   PubMed Web of Science ®Google Scholar
• Baralle FE, Giudice J. Alternative splicing as a regulator of development and tissue identity. Nat Rev Mol Cell Biol. 2017;18:437–451.
   PubMed Web of Science ®Google Scholar
• Braunschweig U, Gueroussov S, Plocik AM, et al. Dynamic integration of splicing within gene regulatory pathways. Cell. 2013;152:1252–1269.
   PubMed Web of Science ®Google Scholar
• Ben-Haim MS, Moshitch-Moshkovitz S, Rechavi G. FTO: linking m6A demethylation to adipogenesis. Cell Res. 2015;25:3–4.
   PubMed Web of Science ®Google Scholar
• Zhao X, Yang Y, Sun BF, et al. FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res. 2014;24:1403–1419.
   PubMed Web of Science ®Google Scholar
• Roundtree IA, Luo GZ, Zhang Z, et al. YTHDC1 mediates nuclear export of N(6)-methyladenosine methylated mRNAs. Elife. 2017;6:pii:e31311.
   Web of Science ®Google Scholar
• Zheng G, Dahl JA, Niu Y, et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell. 2013;49:18–29.
   PubMed Web of Science ®Google Scholar
• Penn JK, Graham P, Deshpande G, et al. Functioning of the Drosophila Wilms’-tumor-1-associated protein homolog, Fl(2)d, in Sex-lethal-dependent alternative splicing. Genetics. 2008;178:737–748.
   PubMed Web of Science ®Google Scholar
• Barbieri I, Tzelepis K, Pandolfini L, et al. Promoter-bound METTL3 maintains myeloid leukaemia by m(6)A-dependent translation control. Nature. 2017;552:126–131.
   PubMed Web of Science ®Google Scholar
• Lesbirel S, Viphakone N, Parker M, et al. The m(6)A-methylase complex recruits TREX and regulates mRNA export. Sci Rep. 2018;8:13827.
   PubMed Web of Science ®Google Scholar
• Xiao W, Adhikari S, Dahal U, et al. Nuclear m(6)A reader YTHDC1 regulates mRNA splicing. Mol Cell. 2016;61:507–519.
   PubMed Web of Science ®Google Scholar
• Manning BD, Toker A. AKT/PKB Signaling: Navigating The Network. Cell. 2017;169:381–405.
   PubMed Web of Science ®Google Scholar
• Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2:489–501.
   PubMed Web of Science ®Google Scholar
• Liu J, Eckert MA, Harada BT, et al. m(6)A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer. Nat Cell Biol. 2018;20:1074–1083.
   PubMed Web of Science ®Google Scholar
• Wang X, Huang N, Yang M, et al. FTO is required for myogenesis by positively regulating mTOR-PGC-1alpha pathway-mediated mitochondria biogenesis. Cell Death Dis. 2017;8:e2702.
   PubMed Web of Science ®Google Scholar
• Quintas-Cardama A, Verstovsek S. Molecular pathways: jak/STAT pathway: mutations, inhibitors, and resistance. Clin Cancer Res. 2013;19:1933–1940.
   PubMed Web of Science ®Google Scholar
• Zanoni I, Granucci F, Broggi A. Interferon (IFN)-lambda takes the helm: immunomodulatory roles of type III IFNs. Front Immunol. 2017;8:1661.
   PubMed Web of Science ®Google Scholar
• Raftery N, Stevenson NJ. Advances in anti-viral immune defence: revealing the importance of the IFN JAK/STAT pathway. Cell Mol Life Sci. 2017;74:2525–2535.
   PubMed Web of Science ®Google Scholar
• Nan Y, Wu C, Zhang YJ. Interplay between Janus Kinase/signal transducer and activator of transcription signaling activated by type I interferons and viral antagonism. Front Immunol. 2017;8:1758.
   PubMed Web of Science ®Google Scholar
• Winkler R, Gillis E, Lasman L, et al. m(6)A modification controls the innate immune response to infection by targeting type I interferons. Nat Immunol. 2018;20:173–182.
   PubMed Web of Science ®Google Scholar
• Rubio RM, Depledge DP, Bianco C, et al. RNA m(6) A modification enzymes shape innate responses to DNA by regulating interferon beta. Genes Dev. 2018;32:1472–1484.
   PubMed Web of Science ®Google Scholar
• Wu R, Liu Y, Zhao Y, et al. m(6)A methylation controls pluripotency of porcine induced pluripotent stem cells by targeting SOCS3/JAK2/STAT3 pathway in a YTHDF1/YTHDF2-orchestrated manner. Cell Death Dis. 2019;10:171.
   PubMed Web of Science ®Google Scholar
• Chen M, Wei L, Law CT, et al. RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2. Hepatology. 2018;67:2254–2270.
   PubMed Web of Science ®Google Scholar
• Li HB, Tong J, Zhu S, et al. m(6)A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways. Nature. 2017;548:338–342.
   PubMed Web of Science ®Google Scholar
• Li M, Zhao X, Wang W, et al. Ythdf2-mediated m(6)A mRNA clearance modulates neural development in mice. Genome Biol. 2018;19:69.
   PubMed Web of Science ®Google Scholar
• Chen J, Liu S, Hu X. Long non-coding RNAs: crucial regulators of gastrointestinal cancer cell proliferation. Cell Death Discov. 2018;4:50.
   Web of Science ®Google Scholar
• Kwok CT, Marshall AD, Rasko JE, et al. Genetic alterations of m(6)A regulators predict poorer survival in acute myeloid leukemia. J Hematol Oncol. 2017;10:39.
   PubMed Web of Science ®Google Scholar
• Bertero A, Brown S, Madrigal P, et al. The SMAD2/3 interactome reveals that TGFbeta controls m(6)A mRNA methylation in pluripotency. Nature. 2018;555:256–259.
   PubMed Web of Science ®Google Scholar
• Li Z, Qian P, Shao W, et al. Suppression of m(6)A reader Ythdf2 promotes hematopoietic stem cell expansion. Cell Res. 2018;28:904–917.
   PubMed Web of Science ®Google Scholar
• Lv J, Zhang Y, Gao S, et al. Endothelial-specific m(6)A modulates mouse hematopoietic stem and progenitor cell development via Notch signaling. Cell Res. 2018;28:249–252.
   PubMed Web of Science ®Google Scholar
• Zhang C, Chen Y, Sun B, et al. m(6)A modulates haematopoietic stem and progenitor cell specification. Nature. 2017;549:273–276.
   PubMed Web of Science ®Google Scholar
• Wu Y, Xie L, Wang M, et al. Mettl3-mediated m(6)A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis. Nat Commun. 2018;9:4772.
   PubMed Web of Science ®Google Scholar
• Cheng M, Sheng L, Gao Q, et al. The m(6)A methyltransferase METTL3 promotes bladder cancer progression via AFF4/NF-kappaB/MYC signaling network. Oncogene. 2019. [Epub ahead of print].
   Google Scholar
• Wahle E, Ruegsegger U. 3’-End processing of pre-mRNA in eukaryotes. FEMS Microbiol Rev. 1999;23:277–295.
   PubMed Web of Science ®Google Scholar
• Wang X, Huang J, Zou T, et al. Human m(6)A writers: two subunits, 2 roles. RNA Biol. 2017;14:300–304.
   PubMed Web of Science ®Google Scholar
• Valverde R, Edwards L, Regan L. Structure and function of KH domains. Febs J. 2008;275:2712–2726.
   PubMed Web of Science ®Google Scholar
• Konig J, Zarnack K, Rot G, et al. iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nat Struct Mol Biol. 2010;17:909–915.
   PubMed Web of Science ®Google Scholar