2014 Fiscal Year Final Research Report
Gene expression regulation via mRNA surveillance system
| Project/Area Number |
23687025
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Molecular biology
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Project Period (FY) |
2011-04-01 – 2015-03-31
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| Keywords | NMD / mRNA分解 / mRNA代謝 / 翻訳終結 / 遺伝性疾患 |
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| Outline of Final Research Achievements |
The nonsense-mediated mRNA decay (NMD) pathway it acts to selectively identify and degrade mRNAs that contain a premature translation termination codon (PTC), and reduce the accumulation of potentially toxic truncated proteins. SMG-1 plays a critical role in NMD. I demonstrated that phosphorylated-Upf1 recruits the SMG-5:SMG-7 complex to phospho-S1096 to induce ribosome dissociation and induce decapping mediated PTC-mRNA decay. Phospho-Upf1 also recruits SMG-6 endonuclease to phospho-T28 which might be involved in PTC-mRNA end-cleavage. Intriguingly, SMG-6 and the stalk region of the UPF1 helicase domain, along with a contribution from the SQ domain, form a interaction and we also show that this region of the UPF1 helicase domain is critical for SMG6 function and NMD. I also demonstrated that UPF2, can be transferred to UPF1 within SMG-1, inducing UPF2-dependent conformational changes required to activate UPF1 within an SMG-1:UPF1:UPF2 complex.
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| Free Research Field |
分子生物学
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