The coupling mechanism of translation and mRNA degradation regulated by RNA binding protein in response to cell signals

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H04745
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Kindai University
• Principal Investigator: FUJIWARA Toshinobu 近畿大学, 薬学部, 教授 (80362804)
• Co-Investigator(Kenkyū-buntansha): 三嶋 雄一郎 京都産業大学, 総合生命科学部, 准教授 (00557069)
• Research Collaborator: ADACHI shungo
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 翻訳制御 / mRNP / mRNA分解

Outline of Final Research Achievements

We show that ZFP36L1 represses translation initiation, and demonstrate that this effect is independent of deadenylation mediated by the ARE. Strikingly, ZFP36L1-mediated translation repression nevertheless requires interaction between ZFP36L1 and CNOT1. Moreover, the eIF4F complex remains bound to the mRNA even in the presence of ZFP36L1. These observations imply that ZFP36L1-mediated repression of translation initiation differs fundamentally from the mechanism used by miRISC. Moreover, we find that translational repression by ZFP36L1 is also independent of 4EHP, despite this being a key factor for translation repression by ZFP36L. Collectively, our results highlight surprising diversity of regulatory mechanisms used by ARE-BPs and factors that interact with the CCR4/NOT co-factor complex.

Free Research Field

翻訳制御

Academic Significance and Societal Importance of the Research Achievements

AREは炎症性サイトカインmRNAの3'非翻訳領域に存在し、mRNAの運命決定およびタンパク質合成量を厳密に制御する。これまでの知見では、AREはRNA結合タンパク質に認識され、多くの場合脱アデニル化複合体を介したpolyA鎖の分解を基点にmRNA分解が誘導される。一方、これらARE結合タンパク質による翻訳制御機構に関する知見はこれまで乏しかった。本研究課題の遂行により、ARE結合タンパク質による翻訳抑制はpolyA鎖の分解とは独立に起こること、そして、その分子機構には脱アデニル化複合体の構成因子が必要であることが明らかになった。