Research Article

Cap-specific terminal N6-methylation of RNA by an RNA polymerase II–associated methyltransferase

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Science  22 Nov 2018:
eaav0080
DOI: 10.1126/science.aav0080

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Abstract

N6-methyladenosine (m6A), a major modification of mRNAs, plays critical roles in RNA metabolism and function. In addition to the internal m6A, N6, 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 Ser5-phosphorylated C-terminal domain of RNA polymerase II, as cap-specific adenosine methyltransferase (CAPAM) responsible for N6-methylation of m6Am. Crystal structure of CAPAM in complex with substrates revealed the molecular basis of cap-specific m6A formation. A transcriptome-wide analysis revealed that N6-methylation of m6Am promotes the translation of capped mRNAs. Thus, a cap-specific m6A writer promotes translation of mRNAs starting from m6Am.

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