m7GTP cap-mediated translation control

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16516
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Nagoya University
• Principal Investigator: Hamaguchi Tomonari 名古屋大学, 医学系研究科, 特任助教 (90812149)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: GEMIN4 / mRNA / m7GTP

Outline of Final Research Achievements

We identified GEMIN4-binding proteins under arsenic state by LC/MS/MS. Binding of endogenous GEMIN4 to m7GTP was promoted by arsenite and methyl methanesulfonate and inhibited by methylation inhibitors. Using reporter assays and the pulsed SILAC method, we obtained data showing that GEMIN4 suppressed translation or protein degradation in an arsenic concentration-dependent manner. However, Ribosomal profiling, performed in collaboration with a collaborator, did not provide data supporting translational repression. In general, GEMIN4 bound to m7GTP cap of mRNA via methylation reaction. However, the biological significance remains unresolved.

Free Research Field

分子生物

Academic Significance and Societal Importance of the Research Achievements

ストレス応答におけるm7GTP cap の動静はわかっていなかった。ヒ素ストレスにてGEMIN4とm7GTPの結合が示唆された。本研究では、GEMIN4とmRNAの関係に注目して解析を始めた。ヒ素ストレスがGEMIN4のメチル化修飾を介して、m7GTPとGEMIN4の結合が進むことが明らかとなった。ストレス下におけるGEMIN4と相互作用するタンパク質を明らかにした。