PUBLICATION
Cap-specific terminal N6-methylation of RNA by an RNA polymerase II-associated methyltransferase
- Authors
- Akichika, S., Hirano, S., Shichino, Y., Suzuki, T., Nishimasu, H., Ishitani, R., Sugita, A., Hirose, Y., Iwasaki, S., Nureki, O., Suzuki, T.
- ID
- ZDB-PUB-200522-32
- Date
- 2019
- Source
- Science (New York, N.Y.) 363(6423): (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Transcription Initiation Site
- Humans
- Methylation
- Nuclear Proteins/chemistry*
- RNA Polymerase II/chemistry*
- RNA Caps/chemistry*
- Mass Spectrometry
- HEK293 Cells
- Methyltransferases/chemistry*
- Gene Knockout Techniques
- Protein Biosynthesis
- Adaptor Proteins, Signal Transducing/chemistry*
- Protein Domains
- PubMed
- 30467178 Full text @ Science
Citation
Akichika, S., Hirano, S., Shichino, Y., Suzuki, T., Nishimasu, H., Ishitani, R., Sugita, A., Hirose, Y., Iwasaki, S., Nureki, O., Suzuki, T. (2019) Cap-specific terminal N6-methylation of RNA by an RNA polymerase II-associated methyltransferase. Science (New York, N.Y.). 363(6423):.
Abstract
N6-methyladenosine (m6A), a major modification of messenger RNAs (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 serine-5-phosphorylated carboxyl-terminal domain of RNA polymerase II, as a cap-specific adenosine methyltransferase (CAPAM) responsible for N6-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 N6-methylation of m6Am promotes the translation of capped mRNAs. Thus, a cap-specific m6A writer promotes translation of mRNAs starting from m6Am.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping