Fine-tuning of translation regulation system by RNA-binding proteins

2015 Fiscal Year Final Research Report

• Project/Area Number: 25291007
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Kinki University (2015); Nagoya City University
• Principal Investigator: FUJIWARA Toshinobu 近畿大学, 薬学部, 教授 (80362804)
• Co-Investigator(Kenkyū-buntansha): TOMARI Yukihide 東京大学, 分子細胞生物学研究所, 教授 (90447368)
• Co-Investigator(Renkei-kenkyūsha): TAKIZAWA Naoki (公財)微生物化学研究会, 微生物化学研究所, 研究員 (50448502)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 翻訳制御 / microRNA / RNA結合タンパク質

Outline of Final Research Achievements

We showed that miRNA inhibits translation of the target mRNA in a deadenylation- and PABP-independent
manner at early time points (PNAS 2012)We next assessed the effect of miRISC on synergistic recruitment of translation initiation factors to target mRNAs by using direct biochemical assays. We show that miRISC promotes the release of both eIF4AI and eIF4AII but not eIF4E and eIF4G from target mRNAs and demonstrate that this is independent of deadenylation. Strikingly, both, the miRISC-induced release of eIF4A I and II from the cap binding complex (CBC) and the miRISC-induced inhibition of cap-dependent translation can be counteracted by the RNA binding protein HuD via a direct interaction of HuD with eIF4A. In summary, we propose that eIF4A I and II are key targets in the translation initiation control mechanisms by miRISC. These results were reported in Molecular Cell (2014).

Free Research Field

RNA生化学