2. Academic Validation
  3. Cap-specific terminal N 6-methylation of RNA by an RNA polymerase II-associated methyltransferase

Cap-specific terminal N 6-methylation of RNA by an RNA polymerase II-associated methyltransferase

  • Science. 2019 Jan 11;363(6423):eaav0080. doi: 10.1126/science.aav0080.
Shinichiro Akichika 1,  Seiichi Hirano 2,  Yuichi Shichino 3,  Takeo Suzuki 1,  Hiroshi Nishimasu 2,  Ryuichiro Ishitani 2,  Ai Sugita 4,  Yutaka Hirose 4,  Shintaro Iwasaki 3 5,  Osamu Nureki 6,  Tsutomu Suzuki 7
Affiliations

Affiliations

  • 1 Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
  • 2 Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
  • 3 RNA System Biochemistry Laboratory, Cluster for Pioneering Research, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • 4 Laboratory of Gene Regulation, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
  • 5 Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo 277-8562, Japan.
  • 6 Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ts@chembio.t.u-tokyo.ac.jp nureki@bs.s.u-tokyo.ac.jp.
  • 7 Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. ts@chembio.t.u-tokyo.ac.jp nureki@bs.s.u-tokyo.ac.jp.
PMID: 30467178 DOI: 10.1126/science.aav0080
Abstract

N 6-methyladenosine (m6A), a major modification of messenger RNAs (mRNAs), plays critical roles in RNA metabolism and function. In addition to the internal m6A, N 6, 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 N 6-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 N 6-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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