Investigation of novel polypeptide chain releasing factors in Drosophila cells

Research Project

Project/Area Number	26840001
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Molecular biology
Research Institution	The University of Tokyo
Principal Investigator	KASHIMA Isao 東京大学, 教養学部, 特任准教授 (60613180)
Project Period (FY)	2014-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	translation / termination / ribosome / mRNA分解 / 翻訳終結
Outline of Final Research Achievements	Nonstop mRNA decay (NSD) is quality-control mechanism that detects and degrades mRNAs lacking stop codons. Nonstop protein degradation (NSPD) eliminates aberrant proteins derived from nonstop mRNA. The previous studies in yeast indicate that the Dom34:Hbs1 complex, which are paralogues of mammalian eRF1:eRF3 complex, promotes peptidyle-tRNA release and stalled ribosome dissociation by binding to the empty A site of the stalled ribosome. This enables access of the Ski:Exosome exonuclease complex at 3' end of nonstop mRNAs for subsequent NSD. The E3 ubiquitin ligase Ltn1 is responsible for proteasome-dependent aberrant nonstop polypeptides degradation (NSPD) following the dissociation of ribosome. This study showed that Pelota (Dom34 paralog) and Hbs1 are involved in the degradation of nonstop mRNAs and Ltn1 is essential for NSPD via proteasome pathway in Drosophila Melanogaster cells.