|Budget Amount *help
¥27,170,000 (Direct Cost: ¥20,900,000、Indirect Cost: ¥6,270,000)
Fiscal Year 2014: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2013: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2012: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2011: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
|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.