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2002 Fiscal Year Final Research Report Summary

Quality Control of mRNA

Research Project

Project/Area Number 13680767
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionKyushu University

Principal Investigator

HAYAKAWA Hiroshi  Kyushu University, Department of Medical Biochemistry, Assistant Prof., 医学研究院, 助手 (70150422)

Project Period (FY) 2001 – 2002
KeywordsOxidative stress / Transcriptonal error / Abnormal protein / RNA binding protein / Aging
Research Abstract

Previosly we found that the persistence of oxidized guanine residues in messenger RNA caouses translational errors in Eschericha coli cells and, as the result, abnormal protein is produced [Science 278, 128-130. 1997]. To counteract, organisms possess a mechanism to prevent misincorporation of 8-oxoguanine, an oxidized form of guanine residue, into nascent RNA. E. coli MutT protein hydrolyzes 8-oxoGTP, an oxidized GTP as substrate for erroneous RNA synthesis, thereby suppressing the misincorporation. However, when guanine residues in RNA are oxidized, the mechanism is totally useless. One can, therefore, assume that organisms probably have another mechanism for recognizing RNA molecules carrying 8-oxoguanine and prevent the RNA from entering into the cellular translation machinery.
In this present project we found that E. coli and human cells possess proteins that bind specifically to RNA containing 8-oxoguanine. PNP protein of E. coli (Biochemistry 2001) and YB-1 proteins of human (Biochemistry 2002) are identified as such binding proteins. E. coli mutants defective in the enzyme become super-resistant to paraquat, a well-known drug inducing oxidative stress. These proteins may function to discriminate oxidized and normal RNA molecules, this maintaining a high fidelity of translation.

  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] H.Hayakawa, T.Uchiumi, T.Fukuda, M.Ashizuka, K.Kohno, M.Kuwano, Mutsuo Sekiguchi: "Binding Capacity of Human YB-1 Protein for RNA Containing 8-Oxoguanine"Biochemistry. 41. 12739-12744 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Takahashi, F.Maraboeuf, Y.Sasaki, H.Yakushiji, M.Mishima, M.Shirakawa, S.Iwai, H.Hayakawa, M.Sekiguchi, Y.Nakabeppu: "Role of tryptophane residues in the recognition of mutagenic oxidized nucleotides by human antimutator MTH1 protein"J.M.B.. 319. 129-139 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Hayakawa, M.Kuwano, M.Sekiguchi: "Specific Binding of 8-Oxoguanine-containing RNA to Polynucleotide Phosphorylase Protein"Biochemistry. 40. 9977-9982 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Hayakawa., T.Uchiumi., T.Fukuda., M.Ashizuka., K.Kohno., M.Kuwano., and Mutsuo Sekiguchi.: "Binding Capacity of Human YB-1 Protein for RNA Containing 8-Oxoguanine"Biochemistry. 41. 12739-12744 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Takahashi., F.Maraboeuf., Y.Sasaki., H.Yakushiji., M.Mishima., M.Shirakawa., S.Iwai., H.Hayakawa., M.Sekiguchi., and Y.Nakabeppu.: "Role of tryptophane residues in the recognition of mutagenic oxidized nucleotides by human antimutator MTH1 protein"J. M. B.. 319. 129-139 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Hayakawa., M.Kuwano., and M.Sekiguchi.: "Specific Binding of 8-Oxoguanine-containing RNA to Polynucleotide Phosphorylase Protein"Biochemistry. 40. 9977-9982 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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