mRNA (2'-O-methyladenosine-N(6)-)-methyltransferase
mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity
Cap-specific terminal <i>N</i> <sup>6</sup>-methylation of RNA by an RNA polymerase II-associated methyltransferase.
<i>N</i> <sup>6</sup>-methyladenosine (m<sup>6</sup>A), a major modification of messenger RNAs (mRNAs), plays critical roles in RNA metabolism and function. In addition to the internal m<sup>6</sup>A, <i>N</i> <sup>6</sup>, 2'-<i>O</i>-dimethyladenosine (m<sup>6</sup>Am) 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 <i>N</i> <sup>6</sup>-methylation of m<sup>6</sup>Am. The crystal structure of CAPAM in complex with substrates revealed the molecular basis of cap-specific m<sup>6</sup>A formation. A transcriptome-wide analysis revealed that <i>N</i> <sup>6</sup>-methylation of m<sup>6</sup>Am promotes the translation of capped mRNAs. Thus, a cap-specific m<sup>6</sup>A writer promotes translation of mRNAs starting from m<sup>6</sup>Am.