期刊
SCIENCE
卷 363, 期 6423, 页码 141-141出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aav0080
关键词
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资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT)
- Japan Society for the Promotion of Science (JSPS) [26113003, 26220205, 18H05272, 21115003, 18K19141, 17K07282, JP17H05679, JP17H04998]
- Japan Agency for Medical Research and Development (AMED)
- NIH [S10 OD018174]
- Bioinformatics Analysis Environment Service on RIKEN Cloud at RIKEN Advanced Center for Computing and Communications
- Grants-in-Aid for Scientific Research [17K07282, 18K19141, 21115003] Funding Source: KAKEN
N-6-methyladenosine (m(6)A), a major modification of messenger RNAs (mRNAs), plays critical roles in RNA metabolism and function. In addition to the internal m(6)A, N-6, 2'-O-dimethyladenosine (m(6)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 N-6-methylation of m(6)Am. The crystal structure of CAPAM in complex with substrates revealed the molecular basis of cap-specific m(6)A formation. A transcriptome-wide analysis revealed that N-6-methylation of m(6)Am promotes the translation of capped mRNAs. Thus, a cap-specific m(6)A writer promotes translation of mRNAs starting from m(6)Am.
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