Neuronal activity-dependent translation regulation by the polyampholytic IDR of eIF3a

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19281
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: National Institutes of Natural Sciences
• Principal Investigator: Shiina Nobuyuki 大学共同利用機関法人自然科学研究機構(機構直轄研究施設), 生命創成探究センター, 准教授 (30332175)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: RNA顆粒 / 天然変性領域 / IDR / eIF3a / 神経活動 / 流動性 / 局所翻訳

Outline of Final Research Achievements

During evolution, the eukaryotic translation initiation factor 3a (eIF3a) in vertebrates has acquired a long intrinsically disordered region (vIDR) of approximately 400 amino acids at its C-terminus. This vIDR suppresses the mobility of eIF3a within neuronal RNA granules and is involved in the regulation of local translation through activity-dependent increases in mobility. In this study, we analyzed the similarities and differences between the repeat sequence region in the first half of the vIDR (vIDR1) and the random sequence region in the second half of the vIDR (vIDR2). Contrary to our initial hypothesis that the function of the vIDR depends solely on its amino acid composition and length, and not on its sequence, our findings suggest that the differences between the repeat and random sequences in vIDR1 and vIDR2 are crucial.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

天然変性領域（IDR）は、弱い相互作用を介して液-液相分離し、非膜オルガネラの形成やダイナミクスを制御する。しかし、IDRのアミノ配列は種間で保存性が低く、その配列の重要性については未解明な部分が多い。eIF3aのvIDR1とvIDR2は、アミノ酸組成は類似しているが、リピートとランダムという配列上の相違点がある。本研究で得られたこの2つの領域の配列の違いがvIDRの機能において重要であるという知見は、IDRの配列ルールの解明に向けて重要なものであり、大きな学術的意義を持つ。