Analysis of the generation of a novel small RNAs by mRNA surveillance in eukaryote cells

• Project/Area Number: 24770162
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Molecular biology
• Research Institution: Tohoku University
• Principal Investigator: KASHIMA ISAO 東北大学, 薬学研究科(研究院), 助教 (60613180)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: Nonstop mRNA decay / mRNA品質管理 / samll RNA / mRNA surveillance / Ribosome

Research Abstract

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. Here we show that Pelota (Dom34 paralog) and Hbs1 are involved in the degradation of nonstop mRNAs in showed as well as distinct manners compared with yeast, and Ltn1 is essential for NSPD via proteasome pathway in Drosophila Melanogaster cells.