2006 Fiscal Year Final Research Report Summary
Messenger RNA regulation by 5'-cap structure
| Project/Area Number |
14035104
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kitasato University |
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Principal Investigator |
MIZUMOTO Kiyohisa Kitasato University, Professor Emeritus, Vice-President (80092344)
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| Co-Investigator(Kenkyū-buntansha) |
INADA Toshifumi Nagoya University, Dpt. ofMol. Biol, Associate professor (40242812)
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| Project Period (FY) |
2002 – 2006
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| Keywords | cap structure / RNA polvmerase II / RNA-dependent RNA polymerase / Sendai virus / Influenza virus / mRNA surveillance aystem / translation repression / プロテアソーム |
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| Research Abstract |
(A) Enzyme mechanisms of mRNA cap formation in eukaryotes as well as negative-strand RNA viruses have been studied. 1) We have shown that the phosphorylation of RNA polymerase II carboxyl terminal domain (CTD) by TFIIH-associated CTD kinase (CAK) is important for successful capping of nascent RNA chain. Using an in vitro transcription system with immobilized template, we demonstrated that capping occurs when the nascent RNA chain grows to 18-19 nt in length. 2) We demonstrated that SeV RNA-dependent RNA polymerase (RdRP) L protein catalyzes cap methylation of virus specific mRNA. This is to our knowledge the first direct biochemical evidence to show that mononegavirus L protein catalyszes cap G-7-methylation. 3) The influenza virus (FluV) RdRP exhibits a cap-dependent endonuclease activity, which cleaves host mRNAs to produce capped RNA fragments with 11 to13 nucleotides. The resulting capped RNA fragments serve as a primer to initiate viral mRNA synthesis. We found that Flu-A and -B endonucleases exhibited different substrate specificities with regard to the extent as well as the position of cap methylation.
(B) A novel mRNA surveillance for mRNA lacking a termination codon (nonstop mRNA) has been proposed in which Ski7p is thought to recognize stalled ribosomes at the 3' end of mRNA. We found that the level of protein product of nonstop mRNA containing a poly(A) tail was reduced 100-fold, and this reduction was due to rapid mRNA degradation, translation repression and protein destabilization, at least in part, by the proteasome. Insertion of a poly(A) tract upstream of a termination codon resulted in translation repression and protein destabilization but not rapid mRNA decay. We propose that translation of the poly(A) tail plays crucial roles in nonstop mRNA surveillance via translation repression and protein destabilization.
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Research Products
(83 results)
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[Journal Article] Characterization of monoclonal antibodies directed against the canine distemper virus nucleocapsid protein.2006
Author(s)
Masuda。M., Sato, H., Kamata, H., Katsuo, T., Takenaka, A., Miura。R., Yoneda, M., Tsukiyama-Kohara。K., Mizumoto. K. & Kai C
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Journal Title
Comp. Immunol. Microbiol. Infect. Dis. 29
Pages: 157-165
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Characterization of monoclonal antibodies directed against the canine distemper virus nucleocapsid protein.2006
Author(s)
Masuda, M, Sato, H., Kamata, H., Katsuo, T., Takenaka, A., Miura, R., Yoneda, M., Tsukiyama-Kohara, K., Mizumoto. K. & Kai, C.
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Journal Title
Comp. Immunol. Microbiol. Infect. Dis. 29
Pages: 157-165
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The ARF tumor suppressor inhibits BCL6-mediated transcriptionalrepression.2005
Author(s)
Suzuki, H., Kurita, M., Mizumoto. K., Moriyama, M., Aiso, S., Nishimoto, I., Matsuoka, M.
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Journal Title
Biochem. Biophys. Res. Commun 326
Pages: 242-248
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Molecular determinants for subcellular localization of hepatitis C virus core protein.2005
Author(s)
Suzuki, R., Sakamoto, S., Tsutsumi, T., Rikimaru, A., Tanaka, K., Shimoike, T., Moriishi, K., Iwasaki, T., Mizumoto. K., Matsuura, Y, Miyamura, T., Suzuki, T.
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Journal Title
J. Virol、 79
Pages: 1271-1281
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] The ARF tumor suppressor inhibits BCL6-mediated transcriptional repression.2005
Author(s)
Suzuki, H., Kurita, M., Mizunioto. K., Moriyama, M., Aiso, S., Nishimoto, I. & Matsuoka, M.
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Journal Title
Biochem. Biophys Res. Commun. 326
Pages: 242-248
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Molecular determinants for subcellular localization of hepatitis C virus core protein.2005
Author(s)
Suzuki, R., Sakamoto, S., Tsutsumi, T., Rikimaru, A., Tanaka, K., Shimoike, T., Moriishi, K., Iwasaki, T., Mizumoto. K., Matsuura, Y., Miyamura, T. & Suzuki, T.
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Journal Title
J. Virol. 79
Pages: 1271-1281
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Overexpression of CR/periphilin downregulates Cdc7 expression and inducesS-phase arrest.2004
Author(s)
Kurita. M., Suzuki, H., Masai, H., Mizumoto. K.. Ogata, E., Nishimoto, I., Aiso, S., Matsuoka, M.
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Journal Title
Biochem. Biophys. Res. Commun. 324
Pages: 554-561
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Overexpression of CR/periphilin downregulates Cdc7 expression and in duces S-phase arrest.2004
Author(s)
Kurita, M., Suzuki, H., Masai, H., Mizumoto, K., Ogata, E., Nishimoto, I., Aiso, S. & Matsuoka, M.
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Journal Title
Biochem. Bwphys. Res. Commun. 324
Pages: 554-561
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] pl9ARF-induced p53-independent apoptosis largely occurs through BAX.2003
Author(s)
Suzuki, H., Kurita, M., Mizumoto. K., Nishimoto, I., Ogata, E., Matsuoka, M.
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Journal Title
Biochem. Biophys. Res. Commun. 312
Pages: 1273-1277
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] p53-independent apoptosis is induced by the pl9ARF tumor suppressor.2002
Author(s)
Tsuji, K., Mizumoto. K., Sudo, H., Kouyama, K., Ogata, E., Matsuoka, M.
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Journal Title
Biochem. Biophys. Res. Commun 295
Pages: 621-629
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Proteomic analysis of human brain identifies -enolase as a novel autoantigen in Hashimoto's encephalopathy.2002
Author(s)
Ochi, H., Horiuchi, I., Araki, N., Toda, T., Araki, T., Sato, K., Murai, H., Osoegawa, M., Yamada, T., Okamura, K., Ogino, T., Mizumoto. K., Yamashita, H., Saya, H., J. Kira
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Journal Title
FEBS Lett 528
Pages: 197-202
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Interaction of S-adenosylhomocysteine hydrolase of Xenopus laevis withmRNA(guanine-7-)methyltransferase : Implication on its nuclear compartmentalisation and on cap methvlation of hnRNA.2002
Author(s)
Radomski, N., Barreto, G., Kaufmann, C, Yokosuka, J., Mizumoto, K. & Dreyer, C.
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Journal Title
Biochem. Biophys. Acta 1590
Pages: 93-102
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] One-Step affinity purification of the yeast ribosome and its associated proteins and mRNAs.2002
Author(s)
Inada. T., Winstall, E., Tarun, S. Z., Jr., Yates, J. R., 3rd, Schieltz, D., Sachs, A. B.
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Journal Title
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Proteomic analysis of human brain identifies -enolase as a novel autoantigen in Hashimoto's encephalopathy.2002
Author(s)
Ochi, H., Horiuchi, I., Araki, N., Toda, T., Araki, T., Sato, K., Murai, H., Osoegawa, M., Yamada, T., Okamura, K., Ogino, T., Mizumoto. K., Yamashita, H., Saya, H., J. Kira
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Journal Title
FEBS Lett. 528
Pages: 197-202
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] One-step affinity purification of the yeast ribosome and its associated proteins and mRNAs.2002
Author(s)
Inada. T., Winstall, E., Tarun, S. Z., Jr., Yates, J. R., 3rd, Schieltz, D., Sachs, A. B.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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