Publication Date:
2018
Description:
〈p〉〈i〉N〈/i〉〈sup〉6〈/sup〉-methyladenosine (m〈sup〉6〈/sup〉A), a major modification of 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 Ser5-phosphorylated C-terminal domain of RNA polymerase II, as cap-specific adenosine methyltransferase (CAPAM) responsible for 〈i〉N〈/i〉〈sup〉6〈/sup〉-methylation of m〈sup〉6〈/sup〉Am. 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.〈/p〉
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Natural Sciences in General
