| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
Cells have surveillance systems that recognize and eliminate aberrant mRNAs to avoid the production of potentially harmful protein products. It is well established that mRNA containing a premature termination codon is eliminated by NMD (nonsense-mediated mRNA decay). There are more examples of aberrant mRNA in cells, including mRNA lacking a termination codon (nonstop mRNA). In eubacteria, ribosomes that have stalled at the 3' end of nonstop mRNA are recycled by tmRNA, a unique molecule that has properties of both tRNA and mRNA. We have recently found the tmRNA quality control system not only degrades aberrant polypeptides but also prevents its production through a rapid elimination of damaged mRNAs. We've also shown that ribosome stalling by the arrest sequence induces mRNA cleavage near the arrest point, resulting in nonstop mRNAs that are recognized by tmRNA.
A novel mRNA surveillance for nonstop mRNA has been proposed in S. cerevisiae. We have shown that ribosome stalling at 3' end of nonstop mRNA blocks further rounds of translation, and the removal of Pab 1p, a poly(A) binding protein, from the poly(A) tail causes accelerated decapping and degradation of nonstop mRNA, in addition to the Ski7p-dependent 3'-to-5' degradation pathway. These indicate that the production of abnormal proteins derived from nonstop mRNA is repressed by different mechanisms between prokaryotes and eukaryotes. In prokaryotes, translation of nonstop mRNA is not repressed, and aberrant proteins should be eliminated by tmRNA-dependent protein degradation. In eukaryotes, translation of nonstop mRNA is repressed, and it may explain the reason why no RNA having an equivalent function to tmRNA has been identified.
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