2,905
Views
10
CrossRef citations to date
0
Altmetric
Review

m6A RNA modification in transcription regulation

, & ORCID Icon
Pages 266-276 | Received 31 Dec 2021, Accepted 18 Mar 2022, Published online: 05 Apr 2022

References

  • Yue Y, Liu J, He C. RNA N 6 -methyladenosine methylation in post-transcriptional gene expression regulation. Genes Dev. 2015;29(13):1343–1355.
  • Frye M, Haranda T, Behm B, et al. RNA modifications modulate gene expression during development. Science. 2018;361(80):1346–1349.
  • Dominissini D, Nachtergaele S, Moshitch-Moshkovitz S, et al. The dynamic N1 -methyladenosine methylome in eukaryotic messenger RNA. Nature. 2016;530(7591):441–446.
  • Linder B, Grozhik AV, Olarerin-George AO, et al. Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome. Nat Methods. 2015;12(8):767–772.
  • Kan L, Grozhik AV, Vedanayagam J, et al. The m 6 A pathway facilitates sex determination in Drosophila. Nat Commun. 2017;8(1):1–16.
  • Worpenberg L, Paolantoni C, Longhi S, et al. Ythdf is a N6-methyladenosine reader that modulates Fmr1 target mRNA selection and restricts axonal growth in Drosophila. EMBO J. 2021;40(4):1–20.
  • Zhou J, Wan J, Shu XE, et al. N6-Methyladenosine guides mRNA alternative translation during integrated stress response. Mol Cell. 2018;69(4):636–647.e7.
  • Dominissini D, Moshitch-Moshkovitz S, Salmon-Divon M, et al. Transcriptome-wide mapping of N6-methyladenosine by m 6A-seq based on immunocapturing and massively parallel sequencing. Nat Protoc. 2013;8(1):176–189.
  • Meyer KD, Saletore Y, Zumbo P, et al. Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell. 2012;149(7):1635–1646.
  • Shulman Z, Stern-Ginossar N. The RNA modification N 6-methyladenosine as a novel regulator of the immune system. Nat Immunol. 2020;21(5):501–512.
  • Schwartz S. Cracking the epitranscriptome. RNA. 2016;22(2):169–174.
  • Patil DP, Chen CK, Pickering BF, et al. M6 A RNA methylation promotes XIST-mediated transcriptional repression. Nature. 2016;537(7620):369–373.
  • Uranishi H, Zolotukhin AS, Lindtner S, et al. The RNA-binding motif protein 15B (RBM15B/OTT3) acts as cofactor of the nuclear export receptor NXF1. J Biol Chem. 2009;284(38):26106–26116.
  • Zolotukhin AS, Uranishi H, Lindtner S, et al. Nuclear export factor RBM15 facilitates the access of DBP5 to mRNA. Nucleic Acids Res. 2009;37(21):7151–7162.
  • 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 m 6 A machinery component Wtap/Fl(2)d. Genes Dev. 2018;32(5–6):415–429.
  • Xu C, Liu K, Tempel W, et al. Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single-stranded N6-methyladenosine RNA demethylation. J Biol Chem. 2014a;289(25):17299–17311.
  • 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(1):18–29.
  • Xu C, Wang X, Liu K, et al. Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain. Nat Chem Biol. 2014b;10(11):927–929.
  • Xu C, Liu K, Ahmed H, et al. Structural basis for the discriminative recognition of N6-Methyladenosine RNA by the human YT521-B homology domain family of proteins. J Biol Chem. 2015;290(41):24902–24913.
  • Liu N, Dai Q, Zheng G, et al. N6 -methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature. 2015;518(7540):560–564.
  • Zhou KI, Shi H, Lyu R, et al. Regulation of Co-transcriptional Pre-mRNA Splicing by m6A through the Low-Complexity Protein hnRNPG. Mol Cell. 2019;76(1):70–81.e9.
  • Alarcón CR, Goodarzi H, Lee H, et al. HNRNPA2B1 is a mediator of m6A-Dependent Nuclear RNA processing events. Cell. 2015;162(6):1299–1308.
  • Du H, Zhao Y, He J, et al.YTHDF2 destabilizes m 6 A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Commun Nat.2016;7:12626.
  • Shi H, Wang X, Lu Z, et al. YTHDF3 facilitates translation and decay of N 6-methyladenosine-modified RNA. Cell Res. 2017;27(3):315–328.
  • Xiao W, Adhikari S, Dahal U, et al. Nuclear m6A reader YTHDC1 regulates mRNA Splicing. Mol Cell. 2016a;61(4):507–519.
  • Roundtree IA, Luo GZ, Zhang Z, et al. YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs. Elife. 2017;6:1–28.
  • Slobodin B, Han R, Calderone V, et al. Transcription impacts the efficiency of mRNA translation via Co-transcriptional N6-adenosine Methylation. Cell. 2017;169(2):326–337.e12.
  • Ji Q, Zong X, Mao Y, et al. A heat shock–responsive lncRNA Heat acts as a HSF1-directed transcriptional brake via m 6 A modification. Proc Natl Acad Sci U S A. 2021;118(25):1–11.
  • Liu J, Dou X, Chen C, et al. N 6 -methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription. Science. 2020;8(6477):580–586.
  • Lee JH, Wang R, Xiong F, et al. Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation. Mol Cell. 2021;81(16):3368–3385.e9.
  • Sabari BR, Dall’Agnese A, Boija A, et al. Coactivator condensation at super-enhancers links phase separation and gene control. Science. 2018;379(80):361.
  • Nayler O, Hartmann AM, Stamm S. The ER repeat protein YT521-B localizes to a novel subnuclear compartment. J Cell Biol. 2000;150(5):949–961.
  • Brien TO, Hardlnu S, Greenleaft A, et al. Phosphorylation of RNA polymerase lie-terminal elongation. Nature. 1993;75–77.
  • Hsin JP, Manley JL. The RNA polymerase II CTD coordinates transcription and RNA processing. Genes Dev. 2012;26(19):2119–2137.
  • Komarnitsky P, Cho EJ, Buratowski S. Different phosphorylated forms of RNA polymerase II and associated mRNA processing factors during transcription. Genes Dev. 2000;14(19):2452–2460.
  • Lagha M, Bothma JP, Esposito E, et al. XPaused Pol II coordinates tissue morphogenesis in the drosophila embryo. Cell. 2013;153(5):976.
  • Vos SM, Farnung L, Urlaub H, et al. Structure of paused transcription complex Pol II–DSIF–NELF. Nature. 2018a;560(7720):601–606.
  • Vos SM, Farnung L, Boehning M, et al. Structure of activated transcription complex Pol II–DSIF–PAF–SPT6. Nature. 2018b;560(7720):607–612.
  • Akhtar J, Renaud Y, Albrecht S, et al. m6A RNA methylation regulates promoter- proximal pausing of RNA polymerase II. Mol Cell. 2021;81(16):3356–3367.e6.
  • Huang H, Weng H, Zhou K, et al. Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally. Nature; 2019.
  • Prieto C, Nguyen DTT, Liu Z, et al. Transcriptional control of CBX5 by the RNA-binding proteins RBMX and RBMXL1 maintains chromatin state in myeloid leukemia. Nat. Cancer. 2021;2(7):741–757.
  • Xu W, He C, Kaye EG, et al. Dynamic control of chromatin-associated m6A methylation regulates nascent RNA synthesis. Mol Cell. 2022;82:1–13.
  • Chen J, Zhang YC, Huang C, et al. m6A Regulates neurogenesis and neuronal development by modulating histone methyltransferase Ezh2. Genom Proteom Bioinform. 2019;17(2):154–168.
  • Fei Q, Yang X, Jiang H, et al. SETDB1 modulates PRC2 activity at developmental genes independently of H3K9 trimethylation in mouse ES cells. Genome Res. 2015;25(9):1325–1335.
  • Chen C, Liu W, Guo J, et al. Nuclear m6A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos. Protein Cell. 2021;12(6):455–474.
  • Liu J, Gao M, He J, et al. The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity. Nature. 2021;591(7849):322–326.
  • Xu W, Li J, He C, et al. METTL3 regulates heterochromatin in mouse embryonic stem cells. Nature. 2021;591(7849):317–321.
  • 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(2):195–206.
  • 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(7397):201–206.
  • 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(12):1403–1419.
  • Ke S, Pandya-Jones A, Saito Y, et al. m 6 A mRNA modifications are deposited in nascent pre-mRNA and are not required for splicing but do specify cytoplasmic turnover. Genes Dev. 2017;31(10):990–1006.
  • Lewis CJT, Pan T, Kalsotra A. RNA modifications and structures cooperate to guide RNA-protein interactions. Nat Rev Mol Cell Biol. 2017;18(3):202–210.
  • Xiao W, Adhikari S, Xiao W, et al. Nuclear m 6 A Reader YTHDC1 Regulates mRNA Splicing. Mol Cell. 2016b;61:1–13.
  • Mendel M, Delaney K, Pandey RR, et al. Splice site m6A methylation prevents binding of U2AF35 to inhibit RNA splicing. Cell. 2021;184(12):3125–3142.e25.
  • Akhtar J, Kreim N, Marini F, et al. Promoter-proximal pausing mediated by the exon junction complex regulates splicing. Nat Commun. 2019;10(1):521.
  • Ji X, Zhou Y, Pandit S, et al. SR proteins collaborate with 7SK and promoter-associated nascent RNA to release paused polymerase. Cell. 2013;153(4):855–868.
  • Luco RF, Misteli T. More than a splicing code: integrating the role of RNA, chromatin and non-coding RNA in alternative splicing regulation. Curr Opin Genet Dev. 2011;21(4):366–372.
  • Li Y, Xia L, Tan K, et al. N 6-Methyladenosine co-transcriptionally directs the demethylation of histone H3K9me2. Nat Genet. 2020;52(9):870–877.
  • Chen L, Chen JY, Zhang X, et al. R-ChIP using inactive RNase H reveals dynamic coupling of R-loops with transcriptional pausing at gene promoters. Mol Cell. 2017;68(4):745–757.e5.
  • Yang X, Liu QL, Xu W, et al. m6A promotes R-loop formation to facilitate transcription termination. Cell Res. 2019;29(12):1035–1038.
  • Abakir A, Giles TC, Cristini A, et al. N 6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells. Nat Genet. 2020;52(1):48–55.
  • Kang HJ, Cheon NY, Park H, et al. TonEBP recognizes R-loops and initiates m6A RNA methylation for R-loop resolution. Nucleic Acids Res. 2021;49(1):269–284.
  • Hsieh CL, Fei T, Chen Y, et al. Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation. Proc Natl Acad Sci U S A. 2014;111(20):7319–7324.
  • Li W, Notani D, Ma Q, et al. Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature. 2013;498(7455):516–520.
  • Wang D, Garcia-Bassets I, Benner C, et al. Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature. 2011;474(7351):390–397.
  • Vernimmen D. Uncovering enhancer functions using the α-Globin Locus. PLoS Genet. 2014;10. DOI:https://doi.org/10.1371/journal.pgen.1004668
  • Mikhaylichenko O, Bondarenko V, Harnett D, et al. The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription. Genes Dev. 2018;32(1):42–57.
  • Hah N, Murakami S, Nagari A, et al. Enhancer transcripts mark active estrogen receptor binding sites. Genome Res. 2013;23(8):1210–1223.
  • Kaikkonen MU, Spann NJ, Heinz S, et al. Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription. Mol Cell. 2013;51(3):310–325.
  • Kim TK, Hemberg M, Gray JM, et al. Widespread transcription at neuronal activity-regulated enhancers. Nature. 2010;465(7295):182–187.
  • Melo CA, Drost J, Wijchers PJ, et al. ERNAs are required for p53-Dependent enhancer activity and gene transcription. Mol Cell. 2013;49(3):524–535.
  • Vernimmen D, De GM, Sloane-Stanley JA, et al. Long-range chromosomal interactions regulate the timing of the transition between poised and active gene expression. EMBO J. 2007;26(8):2041–2051.
  • Schaukowitch K, Joo JY, Liu X, et al. Enhancer RNA facilitates NELF release from immediate early genes. Mol Cell. 2014;56(1):29–42.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.