◇ 2024年3月7日(木)加齢研セミナーのご案内

日時： 令和6年3月7日（木）午後1時～2時
場所： 加齢研実験研究棟７階セミナー室1
演題： m6A and pseudouridine (Ψ) in vertebrate mRNA
講師： Professor. Dr. Sabastian Leidel
所属： Research Group for RNA Biochemistry Department of Chemistry,
Biochemistry and Pharmaceutical Sciences (DCBP)
University of Bern
Hochschulstrasse 6, Bern, Canton of Bern, 3012, Switzerland
担当： 魏　范研（所属　モドミクス医学分野・内線　8562）
要旨： Chemical RNA modifications affect all aspects of RNA biology, including biogenesis, turnover, and tuning the interactions of RNA molecules. I will present two current stories from my lab involving mRNA and tRNA modifications. First, in collaboration with Sebastian Glatt’s group (Krakow, Poland), we solved the structure of human PUS3 and performed several biochemical assays to understand how the absence of Ψ is associated with disease. Interestingly, our findings strongly argue against a role of PUS3 in mRNA modification, but reveal how the highly conserved PUS3 ensures target specificity. Second, to understand the role of N6-methyladenosine (m6A) during vertebrate development, we deleted Mettl3 in zebrafish. mettl3-/- fish die within the first month after fertilization. We combined RNA-seq and single-cell RNA-seq of Mettl3-/- mutant heads to analyze the molecular phenotypes. Strikingly, genes associated with eye disease are dysregulated and histological analysis revealed significant morphological changes of the mutant retinas, while electroretinography uncovered visual defects. Furthermore, mettl3-/- mutants displayed defects in locomotor activity in automated dark-light transition experiments, a phenotype that worsened over time. Finally, we found that mutant cells respond to the lack of m6A by regulating the splicing of wtap, the scaffold member of the m6A-writer complex.

RNAには多様な転写後修飾が含まれており、転写後の遺伝子発現調節を制御することが生命高次機能に不可欠です。修飾のなかでも、N6-methyladenosine(m6A)修飾やシュードウリジン(Ψ)修飾に対する注目度が特に高く、国際的な競争が激しい分野となっています。本セミナーではRNA修飾研究分野において高名なリーデル教授（スイス、ベルン大学）をお招き、真核生物における最近のRNA修飾研究について講演して頂きます。ぜひご参加いただき、RNA修飾研究の最前線に触れて頂ければと思います。