2005 Fiscal Year Final Research Report Summary
The structure and function of a novel G protein family regulating eukaryotic mRNA dynamics
| Project/Area Number |
13854025
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional biochemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KATADA Toshiaki The University of Tokyo, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学系研究科, 教授 (10088859)
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| Co-Investigator(Kenkyū-buntansha) |
KONTANI Kenji The University of Tokyo, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学系研究科, 助教授 (30302615)
KAJIHO Hiroaki The University of Tokyo, Graduate School of Pharmaceutical Science, Assistant Professor, 大学院・薬学系研究科, 助手 (70401221)
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| Project Period (FY) |
2001 – 2005
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| Keywords | G protein / translation termination / mRNA degradation / signal transduction / poly(A) tail / poly(A) nuclease |
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| Research Abstract |
In eukaryotic protein synthesis, all three termination codons are directly recognized by a polypeptide-chain releasing factor, eRF1,to release polypeptide chain from ribosome, and another releasing factor, eRF3,is required for eRF1 binding to ribosomal A site. We previously reported that a GTP-binding protein, whose carboxy-terminal sequence is homologous to the eukaryotic elongation factor EF1α, forms a complex with eRF1 to function as eRF3 in the translation termination and that eRF3 consists of the EF1α-like carboxy-terminal (C) and amino-terminal (N) domains. In the present studies, we investigated the structures and functions of eRF3 and its related G proteins. The major findings obtained in this study are summarized as follows.
1)The C domain of eRF3 associated with eRF1,whereas the N domain was capable of binding to poly-adenylate binding protein (PABP) associating with the poly(A) tail of mRNAs presumably for their stabilization. 2)When the interaction between eRF3-N domain and PABP was abolished, decay rate of all mRNAs was decreased due to the inhibition of poly(A) tail shortening. 3)We identified a poly(A) nuclease (PAN) complex that is activated by PABP and found that eRF3 and PAN complex competitively bound to PABP. These results indicate that the translation termination-coupled mRNA decay is mediated through eRF3-dependent poly(A) shortening. Thus, eRF3 functions not only as an eRF1-carrier protein in the translation termination but also as an initiator of the mRNA degradation machinery. 4)We also investigated the functions of other G proteins (Ski7 and eRFS) structurally related to eRF3 and found that the N domains of these G proteins commonly interact with factors involved in mRNA-degradation machineries to regulate mRNA stabilization.
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