Research Project
Grant-in-Aid for Challenging Research (Exploratory)
We aimed to elucidate the function of the 5’-terminal N6-methyladenosine (1st-m6A) modification which is found only in vertebrates at the 5’-terminus of mRNA. We successfully identified the gene for the methyltransferase (MTase) for 1st-m6A, confirmed enzymatic methylation activity of the gene product in vitro and determined structural features of mRNA which can accept a N6-methyl group to the 1st-adenosine. Crystal structures of the MTase reveled amino acid residues which are essential to the MTase activity and recognition of substrate mRNA. Knocking out of the MTase gene in cultured cells showed the sensitivity to the oxidative stress. Furthermore, deep-sequencing analyses revealed that 1st-m6A modification contributes to enhance translation efficiency of mRNAs harboring 1st-m6A.
1970年代における始端m6Aの発見以降、生合成や機能が不明なまま約40年が経過していたが、今回、始端m6A修飾の生合成機構や機能的意義の解明にはじめて成功した。始端m6A修飾は我々ヒトを含む脊椎動物で主に見いだされる、生物種分布が特徴的な修飾である。脊椎動物の生物種としての特徴を深く理解する上でも、始端m6A形成メカニズムの解明は一定の意義があると言えるだろう。
All 2019 2018 Other
All Journal Article (2 results) (of which Peer Reviewed: 1 results, Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 2 results, Invited: 1 results) Remarks (1 results)
Science
Volume: 363 Issue: 363 Pages: 1-7
10.1126/science.aav0080
生体の科学
Volume: 69 Pages: 398-399
https://www.t.u-tokyo.ac.jp/soe/press/setnws_201811270918295542170205.html