3,603
Views
32
CrossRef citations to date
0
Altmetric
Research Paper

The dynamics of FTO binding and demethylation from the m6A motifs

, , , ORCID Icon, , ORCID Icon, , , & show all
Pages 1179-1189 | Received 14 Feb 2019, Accepted 09 May 2019, Published online: 31 May 2019

References

  • 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.
  • Perry RP, Kelley DE. Existence of methylated messenger RNA in mouse L cells. Cell. 1974;1:37–42.
  • Furuichi Y. “Methylation-coupled” transcription by virus-associated transcriptase of cytoplasmic polyhedrosis virus containing double-stranded RNA. Nucleic Acids Res. 1974;1:809–822.
  • Rhodes DP, Moyer SA, Banerjee AK. In vitro synthesis of methylated messenger RNA by the virion-associated RNA polymerase of vesicular stomatitis virus. Cell. 1974;3:327–333.
  • Shatkin AJ. Methylated messenger RNA synthesis in vitro by purified reovirus. Proc Natl Acad Sci U S A. 1974;71:3204–3207.
  • Abraham G, Rhodes DP, Banerjee AK. The 5ʹ terminal structure of the methylated mRNA synthesized in vitro by vesicular stomatitis virus. Cell. 1975;5:51–58.
  • Furuichi Y, Miura K-I. A blocked structure at the 5ʹ terminus of mRNA from cytoplasmic polyhedrosis virus. Nature. 1975;253:374.
  • Furuichi Y, Morgan M, Muthukrishnan S, et al. Reovirus messenger RNA contains a methylated, blocked 5ʹ-terminal structure: m-7G(5ʹ)ppp(5ʹ)G-MpCp. Proc Natl Acad Sci U S A. 1975;72:362–366.
  • Wei CM, Gershowitz A, Moss B. 5ʹ-Terminal and internal methylated nucleotide sequences in HeLa cell mRNA. Biochemistry. 1976;15:397–401.
  • Adams JM, Cory S. Modified nucleosides and bizarre 5ʹ-termini in mouse myeloma mRNA. Nature. 1975;255:28–33.
  • Furuichi Y, Morgan M, Shatkin AJ, et al. Methylated, blocked 5 termini in HeLa cell mRNA. Proc Natl Acad Sci U S A. 1975;72:1904–1908.
  • Wei C, Gershowitz A, Moss B. N6, O2ʹ-dimethyladenosine a novel methylated ribonucleoside next to the 5ʹ terminal of animal cell and virus mRNAs. Nature. 1975;257:251–253.
  • Wei CM, Moss B. Nucleotide sequences at the N6-methyladenosine sites of HeLa cell messenger ribonucleic acid. Biochemistry. 1977;16:1672–1676.
  • Canaani D, Kahana C, Lavi S, et al. Identification and mapping of N6-methyladenosine containing sequences in simian virus 40 RNA. Nucleic Acids Res. 1979;6:2879–2899.
  • Meyer KD, Saletore Y, Zumbo P, et al. Comprehensive analysis of mRNA methylation reveals enrichment in 3ʹ UTRs and near stop codons. Cell. 2012;149:1635–1646.
  • 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.
  • Linder B, Grozhik AV, Olarerin-George AO, et al. Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome. Nat Methods. 2015;12:767–772.
  • Jia G, Fu Y, Zhao X, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol. 2011;7:885–887.
  • Munns TW, Liszewski MK, Sims HF. Characterization of antibodies specific for N6-methyladenosine and for 7-methylguanosine. Biochemistry. 1977;16:2163–2168.
  • Bringmann P, Luhrmann R. Antibodies specific for N6-methyladenosine react with intact snRNPs U2 and U4/U6. FEBS Lett. 1987;213:309–315.
  • Fu Y, Jia G, Pang X, et al. FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA. Nat Commun. 2013;4:1798.
  • Wang X, Lu Z, Gomez A, et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature. 2013;505:117–120.
  • Meyer KD, Jaffrey SR. The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat Rev Mol Cell Biol. 2014;15:313–326.
  • 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.
  • Meyer Kate D, Patil Deepak P, Zhou J, et al. 5′ UTR m6A promotes cap-independent translation. Cell. 2015;163:999–1010.
  • Zhou J, Wan J, Gao X, et al. Dynamic m6A mRNA methylation directs translational control of heat shock response. Nature. 2015;526:591–594.
  • Yang Y, Fan X, Mao M, et al. Extensive translation of circular RNAs driven by N6-methyladenosine. Cell Res. 2017;27:626–641.
  • Zheng Q, Hou J, Zhou Y, et al. The RNA helicase DDX46 inhibits innate immunity by entrapping m6A-demethylated antiviral transcripts in the nucleus. Nat Immunol. 2017;18:1094–1103.
  • Chen T, Hao YJ, Zhang Y, et al. m6A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell. 2015;16:289–301.
  • Haussmann IU, Bodi Z, Sanchez-Moran E, et al. m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature. 2016;540:301–304.
  • Ivanova I, Much C, Di Giacomo M, et al. The RNA m6A reader YTHDF2 is essential for the post-transcriptional regulation of the maternal transcriptome and oocyte competence. Mol Cell. 2017;67:1–9.
  • Liu J, Eckert MA, Harada BT, et al. m6A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer. Nat Cell Biol. 2018;20:1074–1083.
  • 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.
  • Li Z, Weng H, Su R, et al. FTO plays an oncogenic role in acute myeloid leukemia as a N6-methyladenosine RNA demethylase. Cancer Cell. 2017;31:127–141.
  • Cui Q, Shi H, Ye P, et al. m6A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells. Cell Rep. 2017;18:2622–2634.
  • Barbieri I, Tzelepis K, Pandolfini L, et al. Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control. Nature. 2017;552:126–131.
  • Su R, Dong L, Li C, et al. R-2HG exhibits anti-tumor activity by targeting FTO/m6A/MYC/CEBPA signaling. Cell. 2018;172:1–16.
  • Zhang C, Samanta D, Lu H, et al. Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA. Proc Natl Acad Sci U S A. 2016;113:E2047–E56.
  • 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.
  • Zhao BS, Nachtergaele S, Roundtree IA, et al. Our views of dynamic N6-methyladenosine RNA methylation. Rna. 2018;24:268–272.
  • Mauer J, Jaffrey SR. FTO, m6Am, and the hypothesis of reversible epitranscriptomic mRNA modifications. FEBS Lett. 2018;592:2012–2022.
  • Darnell RB, Ke S, Darnell JE. Pre-mRNA processing includes N6 methylation of adenosine residues that are retained in mRNA exons and the fallacy of “RNA epigenetics”. Rna. 2018;24:262–267.
  • Rosa-Mercado NA, Withers JB, Steitz JA. Settling the m6A debate: methylation of mature mRNA is not dynamic but accelerates turnover. Genes Dev. 2017;31:957–958.
  • Meyer KD, Jaffrey SR. Rethinking m6A readers, writers, and erasers. Annu Rev Cell Dev Biol. 2017;33:319–342.
  • Fu Y, Dominissini D, Rechavi G, et al. Gene expression regulation mediated through reversible m6A RNA methylation. Nat Rev Genet. 2014;15:293–306.
  • Liu J, Yue Y, Han D, et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol. 2014;10:93–95.
  • Huang Y, Yan J, Li Q, et al. Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5. Nucleic Acids Res. 2015;43:373–384.
  • Zou S, Toh JD, Wong KH, et al. N6-Methyladenosine: a conformational marker that regulates the substrate specificity of human demethylases FTO and ALKBH5. Sci Rep. 2016;6:25677.
  • Zhang X, Wei LH, Wang Y, et al. Structural insights into FTO’s catalytic mechanism for the demethylation of multiple RNA substrates. Proc Natl Acad Sci U S A. 2019;116:2919–2924.
  • Bartosovic M, Molares HC, Gregorova P, et al. N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3ʹ-end processing. Nucleic Acids Res. 2017;45:11356–11370.
  • Wei J, Liu F, Lu Z, et al. Differential m6A, m6Am, and m1A demethylation mediated by FTO in the cell nucleus and cytoplasm. Mol Cell. 2018;71:973–985.
  • Van Nostrand EL, Pratt GA, Shishkin AA, et al. Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP). Nat Methods. 2016;13:508–514.
  • Mauer J, Luo X, Blanjoie A, et al. Reversible methylation of m6Am in the 5ʹ cap controls mRNA stability. Nature. 2017;541:371–375.
  • Uren PJ, Bahrami-Samani E, Burns SC, et al. Site identification in high-throughput RNA-protein interaction data. Bioinformatics. 2012;28:3013–3020.
  • Moore MJ, Zhang C, Gantman EC, et al. Mapping Argonaute and conventional RNA-binding protein interactions with RNA at single-nucleotide resolution using HITS-CLIP and CIMS analysis. Nat Protoc. 2014;9:263–293.
  • Xia H, Chen D, Wu Q, et al. CELF1 preferentially binds to exon-intron boundary and regulates alternative splicing in HeLa cells. Biochim Biophys Acta. 2017;1860:911–921.
  • Ke S, Pandya-Jones A, Saito Y, et al. m6A mRNA modifications are deposited in nascent pre-mRNA and are not required for splicing but do specify cytoplasmic turnover. Genes Dev. 2017;31:990–1006.
  • Liu X, Zou H, Slaughter C, et al. DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell. 1997;89:175–184.
  • Seedorf U, Aberle J. Emerging roles of PPARδ in metabolism. Biochim Biophys Acta. 2007;1771:1125–1131.
  • Tacken PJ, Hofker MH, Havekes LM, et al. Living up to a name: the role of the VLDL receptor in lipid metabolism. Curr Opin Lipidol. 2001;12:275–279.
  • Zhou J, Wan J, Shu XE, et al. N6-methyladenosine guides mRNA alternative translation during integrated stress response. Mol Cell. 2018;69:1–12.
  • Zhang S, Zhao BS, Zhou A, et al. m6A demethylase ALKBH5 maintains tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program. Cancer Cell. 2017;31:591–606.
  • Zhang S-Y, Zhang S-W, Liu L, et al. m6A-driver: identifying context-specific mRNA m6A methylation-driven gene interaction networks. PLoS Comp Biol. 2016;12:e1005287.
  • Akichika S, Hirano S, Shichino Y, et al. Cap-specific terminal N6-methylation of RNA by an RNA polymerase II–associated methyltransferase. Science. 2019;363:eaav0080.
  • Shun Z, Zhou‐Lan B, Di X, et al. FTO regulates the chemo‐radiotherapy resistance of cervical squamous cell carcinoma (CSCC) by targeting β-catenin through mRNA demethylation. Mol Carcinog. 2018;57:590–597.
  • Mathiyalagan P, Adamiak M, Mayourian J, et al. FTO-dependent m6A regulates cardiac function during remodeling and repair. Circulation. 2019;139:518–532.
  • Engel M, Eggert C, Kaplick PM, et al. The role of m6A/m-RNA methylation in stress response regulation. Neuron. 2018;99:389–403.
  • Xiang Y, Laurent B, Hsu CH, et al. RNA m6A methylation regulates the ultraviolet-induced DNA damage response. Nature. 2017;543:573–576.
  • Heinz S, Benner C, Spann N, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38:576–589.

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.