Cap-specific terminal N 6-methylation of RNA by an RNA polymerase II-associated methyltransferase - PubMed (original) (raw)
. 2019 Jan 11;363(6423):eaav0080.
doi: 10.1126/science.aav0080. Epub 2018 Nov 22.
Affiliations
- PMID: 30467178
- DOI: 10.1126/science.aav0080
Cap-specific terminal N 6-methylation of RNA by an RNA polymerase II-associated methyltransferase
Shinichiro Akichika et al. Science. 2019.
Abstract
N 6-methyladenosine (m6A), a major modification of messenger RNAs (mRNAs), plays critical roles in RNA metabolism and function. In addition to the internal m6A, N 6, 2'-_O_-dimethyladenosine (m6Am) is present at the transcription start nucleotide of capped mRNAs in vertebrates. However, its biogenesis and functional role remain elusive. Using a reverse genetics approach, we identified PCIF1, a factor that interacts with the serine-5-phosphorylated carboxyl-terminal domain of RNA polymerase II, as a cap-specific adenosine methyltransferase (CAPAM) responsible for N 6-methylation of m6Am. The crystal structure of CAPAM in complex with substrates revealed the molecular basis of cap-specific m6A formation. A transcriptome-wide analysis revealed that N 6-methylation of m6Am promotes the translation of capped mRNAs. Thus, a cap-specific m6A writer promotes translation of mRNAs starting from m6Am.
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Similar articles
- The cap-specific m6A methyltransferase, PCIF1/CAPAM, is dynamically recruited to the gene promoter in a transcription-dependent manner.
Sugita A, Kuruma S, Yanagisawa N, Ishiguro H, Kano R, Ohkuma Y, Hirose Y. Sugita A, et al. J Biochem. 2021 Oct 11;170(2):203-213. doi: 10.1093/jb/mvab032. J Biochem. 2021. PMID: 33982754 - Identification of the m6Am Methyltransferase PCIF1 Reveals the Location and Functions of m6Am in the Transcriptome.
Boulias K, Toczydłowska-Socha D, Hawley BR, Liberman N, Takashima K, Zaccara S, Guez T, Vasseur JJ, Debart F, Aravind L, Jaffrey SR, Greer EL. Boulias K, et al. Mol Cell. 2019 Aug 8;75(3):631-643.e8. doi: 10.1016/j.molcel.2019.06.006. Epub 2019 Jul 3. Mol Cell. 2019. PMID: 31279658 Free PMC article. - Cap-specific, terminal N6-methylation by a mammalian m6Am methyltransferase.
Sun H, Zhang M, Li K, Bai D, Yi C. Sun H, et al. Cell Res. 2019 Jan;29(1):80-82. doi: 10.1038/s41422-018-0117-4. Epub 2018 Nov 28. Cell Res. 2019. PMID: 30487554 Free PMC article. No abstract available. - RNA methyltransferases involved in 5' cap biosynthesis.
Byszewska M, Śmietański M, Purta E, Bujnicki JM. Byszewska M, et al. RNA Biol. 2014;11(12):1597-607. doi: 10.1080/15476286.2015.1004955. RNA Biol. 2014. PMID: 25626080 Free PMC article. Review. - Cap and cap-binding proteins in the control of gene expression.
Topisirovic I, Svitkin YV, Sonenberg N, Shatkin AJ. Topisirovic I, et al. Wiley Interdiscip Rev RNA. 2011 Mar-Apr;2(2):277-98. doi: 10.1002/wrna.52. Epub 2010 Oct 28. Wiley Interdiscip Rev RNA. 2011. PMID: 21957010 Review.
Cited by
- Autophagy of the m6A mRNA demethylase FTO is impaired by low-level arsenic exposure to promote tumorigenesis.
Cui YH, Yang S, Wei J, Shea CR, Zhong W, Wang F, Shah P, Kibriya MG, Cui X, Ahsan H, He C, He YY. Cui YH, et al. Nat Commun. 2021 Apr 12;12(1):2183. doi: 10.1038/s41467-021-22469-6. Nat Commun. 2021. PMID: 33846348 Free PMC article. - RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases.
Willbanks A, Wood S, Cheng JX. Willbanks A, et al. Genes (Basel). 2021 Apr 22;12(5):627. doi: 10.3390/genes12050627. Genes (Basel). 2021. PMID: 33922187 Free PMC article. Review. - Chemo-Enzymatic Modification of the 5' Cap Maintains Translation and Increases Immunogenic Properties of mRNA.
van Dülmen M, Muthmann N, Rentmeister A. van Dülmen M, et al. Angew Chem Int Ed Engl. 2021 Jun 7;60(24):13280-13286. doi: 10.1002/anie.202100352. Epub 2021 May 6. Angew Chem Int Ed Engl. 2021. PMID: 33751748 Free PMC article. - The crosstalk between m6A RNA methylation and other epigenetic regulators: a novel perspective in epigenetic remodeling.
Zhao Y, Chen Y, Jin M, Wang J. Zhao Y, et al. Theranostics. 2021 Mar 4;11(9):4549-4566. doi: 10.7150/thno.54967. eCollection 2021. Theranostics. 2021. PMID: 33754077 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous