Cap-specific terminal N6-methylation of RNA by an RNA polymerase Ⅱ-associated methyltransferase

Authors
Shinichiro Akichika, Seiichi Hirano, Yuichi Shichino, Takeo Suzuki, Hiroshi Nishimasu, Ryuichiro Ishitani, Ai Sugita, Yutaka Hirose, Shintaro Iwasaki, Osamu Nureki, and Tsutomu Suzuki

Abstract
N⁶-methyladenosine (m⁶A), a major modification of 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 Ser5-phosphorylated C-terminal domain of RNA polymerase II, as cap-specific adenosine methyltransferase (CAPAM) responsible for N⁶-methylation of m⁶Am. 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.

Science: http://science.sciencemag.org/content/early/2018/11/19/science.aav0080

Suzuki Lab: http://rna.chem.t.u-tokyo.ac.jp/en/index.html