1999 年度実績報告書

RNA情報機能の分子基盤

研究課題

研究課題/領域番号	09278102
研究機関	東京大学
研究代表者	中村義一東京大学, 医科学研究所, 助教授 (40114590)
研究分担者	松藤千弥東京慈恵医科大学, 医学部, 助教授 (50192753) 口野嘉幸国立がんセンター研究所, 部長(研究職) (60124418) 饗場弘二名古屋大学, 大学院・理学研究所, 教授 (20025662) 横山茂之東京大学, 大学院・理学系研究科, 教授 (00159229) 井上邦夫奈良先端科学技術大学院大学, 助手 (40252415)
キーワード	RNA / 翻訳調節 / 転写後制御 / リボソーム / 分子擬態 / 終止コドン / mRNA動態 / RNA結合蛋白質
研究概要	平成11年度の主要な研究成果を以下に整理して述べる。 1.翻訳調節におけるRNA情報機能の研究:(1)遺伝暗号の中で最後まで解読のメカニズムが明かにされなかった終止コドンの解読機構が解明された。コドン特異的なバクテリア解離因子RF1/RF2の"tripeptides"がtRNAアンチドンと同様に直接終止コドンを識別するペプチド性アンチドンとして働くことが証明された。これは歴史的な発見である。(2)高等動物での試験管内の翻訳終結反応を正確にモニターできる系が作成された。これはフレームシフトと終結反応との競合を利用したアッセイ系で、真核系での精密な翻訳終結とリコーディング機構の解析に突破口を開いた。 2.RNAプロセシング機構の研究:(1)大腸菌tmRNAの標的を検索した結果、野生株においてtmRNA由来のタグが付加されたポリペプチドが多数存在することが明かにされた。これは生理的な条件下でtmRNAによるタグ付加を示した初めての実証である。(2)脊椎動物において神経特異的に発現するRNA結合蛋白質Huが細胞内において核と細胞質の間をシャトルしていることが示唆されてきたが、そのシャトリングに必要な領域を特定し、変異体を利用した解析からHu蛋白質が神経細胞の分化に重要な役割を担っていることが明かにされた。 3.RNA情報構造機能の研究:ショウジョウバエの性決定に係わるSxl蛋白質とその認識配列RNAとの複合体の結晶構造が解かれた。二つのRNA結合ドメインが認識配列を特異的に認識するその仕組は、これまで知られていないRNA/蛋白質の分子認識のメカニズムを明かにしたもので重要な成果である。

研究成果

(32件)

すべてその他

すべて文献書誌 (32件)

[文献書誌] Crawford, D.-J. G., Ito, K., Nakamura, Y., Tate, W. P.: "Indirect regulation of termination efficiency at highly expressed genes and recoding sites by the factor recycling function of Escherichia coli release factor RF3"EMBO J.. 18. 727-732 (1999)
[文献書誌] Ebihara, K., Nakamura, Y.: "C-terminal interaction of translational release factors eRF1 and eRF3 of fission yeast : G-domain uncoupled binding and the role of conserved amino acids"RNA. 5. 739-750 (1999)
[文献書誌] Fujiwara, T., Ito, K., Nakayashiki, T., Nakamura, Y.: "Amber mutations in ribosome recycling factors of Escherichia coli and Thermus thermophilus : evidence for C-terminal modulator element"FEBS Lett.. 447. 297-302 (1999297)
[文献書誌] Yoshimura, K., Ito, K., Nakamura, Y.: "Amber (UAG) suppressors affected in UGA/UAA-specific polypeptide release factor 2 of bacteria : genetic prediction of initial binding to ribosome preceding stop codon recognition"Genes Cells. 4. 253-266 (1999)
[文献書誌] Powell, B., Peters III, H. K., Nakamura, Y., Court, D.: "Cloning and analysis of the rnc-era-recO operon from Pseudomonas aeruginosa"J. Bacteriol.. 181. 5111-5113 (1999)
[文献書誌] Karamyshev, A., Ito, K., Nakamura, Y.: "Polypeptide release factor eRF1 from Tetrahymena thermophila : cDNA cloning, purification and complex formation with yeast eRF3"FEBS Lett.. 457. 483-488 (1999)
[文献書誌] Karamyshev, A., Karamycheva, Z., Ito, K., Matsufuji, S., Nakamura, Y.: "Overexpression and purification of recombinant eRF1 proteins of rabbit and Tetrahymena thermophila"Biochemistry (Moscow). 64. 1648-1658 (1999)
[文献書誌] Wada, M., Nakamura, Y.: "Type-II major-surface-glycoprotein family of Pneumocystis carinii"J. Euk. Microbiol.. 46. 151S-152S (1999)
[文献書誌] Wada, M., Nakamura, Y.: "Immunological characterization of surface subtilisin-like protease (SSP) of Pneumocystis carinii"J. Euk. Microbiol.. 46. 125S-126S (1999)
[文献書誌] Wada, M., Nakamura, Y.: "Type-II major-surface-glycoprotein family of Pneumocystis carinii under the control of novel expression elements"DNA Res.. 6. 211-217 (1999)
[文献書誌] Tin, O. F., Rykunova, A. L., Muranova, T. A., Toyoda, T., Ito, K., Suzuki, T., Watanabe, K., Garber, M. B., Nakamura, Y.: "Proteolytic fragmentation of polypeptide release factor 1 of Thermus thermophilus and crystallization of the stable fragments"Biochimie, In Press. (2000)
[文献書誌] Tanaka, R., Satoh, H., Moriyama, M., Satoh, K., Morishita, Y., Yoshida, S., Watanabe, T., Nakamura, Y., Mori, S.: "Intronic U50 small-nucleolar-RNA (snoRNA) host gene of no protein-coding potential is mapped at the chromosome breakpoint t(3;6)(q27;q15) of human B-cell lymphoma"Genes Cells, In Press. (2000)
[文献書誌] Ito, K., Uno, M., Nakamura, Y.: "A tripeptide 'anticodon deciphers' stop codons in messenger RNA"Nature. 403. 680-683 (200)
[文献書誌] Abe, H., Abo, T., Aiba, H.: "Regulation of intrinsic terminator by translation in Escherichia coli : transcription termination at a distance downstream"Genes to Cells. 4. 87-97 (1999)
[文献書誌] Tagami, H., Aiba, H.: "An inactive open complex mediated by UP element ant Escherichia coli promoter"Proc. Natl. Acad. Sci. USA. 96. 12914-12919 (1999)
[文献書誌] Tanaka, Y., Kimata, K., Inada, T., Tagami, H., Aiba, H.: "Negative regulation of the pts operon by Mls : Mechanism underlying glucose induction in Escherichia coli"Genes to Cells. 4. 391-399 (1999)
[文献書誌] Sugiyama, A., Noguchi, K., Kitanaka, C., Katou, N., Tashiro, F., Ono, T., Yoshida, M. C., Kuchino, Y.: "Molecular cloning and chromosomal mapping of mouse intronless myc gene acting as a potent apoptosis inducer"Gene. 226. 273-283 (1999)
[文献書誌] Mochizuki, T., Kitanaka, C., Noguchi, K., Muramatsu, T., Asai, A., Kuchino, Y.: "Physical and functional interaction between Pim-1 kinase and Cdc25A phosphatase : implication for the Pim-1-mediated activation of the c-Myc signaling pathway"J. Biol. Chem.. 274. 18659-18666 (1999)
[文献書誌] Noguchi, K., Kitanaka, C., Yamana, H., Kokubu, A., Mochizuki, T., Kuchino, Y.: "Regulation of c-Myc through phosphorylation at Ser-62 and -71 by c-Jun N-terminal kinase"J. Biol. Chem.. 274. 32580-32587 (1999)
[文献書誌] Watanabe, S., Muramatsu, T., Ao, H., Hirayama, Y., Takahashi, K., Tanokura, M., Kuchino, Y.: "Molecular cloning of the Lon protease gene form Thermus thermophilus HB8 and characterization of its gene product"E. J. Biochem.. 266. 811-819 (1999)
[文献書誌] Itoh, S., Hattori, T., Hayashi, H., Mizutani, Y., Todo, M., Takii, T., Yang, D., Lee, J. C., Matsufuji, S., Murakami, Y., Chiba, T., Onozaki, K.: "Antiproliferative effect of IL-1 is mediated by p38 mitogen-activated protein kinase in human melanoma cell A 375"J. Immunol.. 162(12). 7434-7440 (1999)
[文献書誌] Murakami, Y., Matsufuji, S., Hayashi, S., Tanahashi, N., Tanaka, K.: "ATP-dependent inactivation and sequestration of ornithine decarboxylase by the 26S proteasome is a prerequisite for degradation"Mol. Cell. Biol.. 19. 7216-7227 (1999)
[文献書誌] Suka, M., Matsufuji, S., Murakami, Y.: "Dietary induction of ornithine decarboxylase in male mouse kidney"Biochim. Biophys. Acta.. 1472. 455-461 (1999)
[文献書誌] Saito, T., Hascilowicz, T., Ohkido, I., Kikuchi, Y., Okamoto, H., Hayashi, S., Murakami, Y., Matsufuji, S.: "Two zebrafish antizymes with different expression and activities"Biochem. J.. 345. 99-106 (2000)
[文献書誌] Isoyama, T., Kamoshita, N., Yasui, K., Iwai, A., Shiroki, K., Toyoda, H., Yamada, A., Takasaki, Y., Nomoto, A.: "Lower concentration of La protein required for internal ribosomal entry onhepatitis C virus RNA than on poliovirus RNA"J. Gen. Virol.. 80(9). 2319-2328 (1999)
[文献書誌] Maegawa, S., Yasuda, K., Inoue, K.: "Maternal mRNA localization of zebrafish DAZ-like gene"Mech. Dev.. 81. 223-226 (1999)
[文献書誌] Handa, N., Nureki, O., et al.: "Structural bases for recognition of the tra mRNA precursor by the Sex-lethal protein"Nature. 398. 579-585 (1999)
[文献書誌] Kigawa, T., et al.: "Cell-free production and stable Oisotope labeling of milligram-quantities of proteins"FEBS Lett.. 442. 15-19 (1999)
[文献書誌] Chi, S.-W., et al.: "Chemical shift perturbation studies of the Interactions of the second RNA-binding domain of the Drosophila Sex-lethal protein with the transformer pre-mRNA polyuridine tract and 3' splice site sequences"Eur. J. Biochem.. 260. 649-660 (1999)
[文献書誌] Chi, S., et al.: "Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells"Oncogene. 18. 2281-2290 (1999)
[文献書誌] Horie, N., et al.: "Modified nucleosides in the first positions of the anticodons of tRNALeu4 and tRNALeu5 from Escherichia coli"Biochemistry. 38. 207-217 (1999)
[文献書誌] Atkins, J. F., Bock, A., Matsufuji, S., Gesteland, R. F.: "Dynamics of the Genetic Code"Cold Spring Habor Laboratory Press. 709 (1999)

1999 年度 実績報告書

RNA情報機能の分子基盤

研究代表者

中村 義一 東京大学, 医科学研究所, 助教授 (40114590)

研究成果

[文献書誌] Crawford, D.-J. G., Ito, K., Nakamura, Y., Tate, W. P.: "Indirect regulation of termination efficiency at highly expressed genes and recoding sites by the factor recycling function of Escherichia coli release factor RF3"EMBO J.. 18. 727-732 (1999)

[文献書誌] Ebihara, K., Nakamura, Y.: "C-terminal interaction of translational release factors eRF1 and eRF3 of fission yeast : G-domain uncoupled binding and the role of conserved amino acids"RNA. 5. 739-750 (1999)

[文献書誌] Fujiwara, T., Ito, K., Nakayashiki, T., Nakamura, Y.: "Amber mutations in ribosome recycling factors of Escherichia coli and Thermus thermophilus : evidence for C-terminal modulator element"FEBS Lett.. 447. 297-302 (1999297)

[文献書誌] Yoshimura, K., Ito, K., Nakamura, Y.: "Amber (UAG) suppressors affected in UGA/UAA-specific polypeptide release factor 2 of bacteria : genetic prediction of initial binding to ribosome preceding stop codon recognition"Genes Cells. 4. 253-266 (1999)

[文献書誌] Powell, B., Peters III, H. K., Nakamura, Y., Court, D.: "Cloning and analysis of the rnc-era-recO operon from Pseudomonas aeruginosa"J. Bacteriol.. 181. 5111-5113 (1999)

[文献書誌] Karamyshev, A., Ito, K., Nakamura, Y.: "Polypeptide release factor eRF1 from Tetrahymena thermophila : cDNA cloning, purification and complex formation with yeast eRF3"FEBS Lett.. 457. 483-488 (1999)

[文献書誌] Karamyshev, A., Karamycheva, Z., Ito, K., Matsufuji, S., Nakamura, Y.: "Overexpression and purification of recombinant eRF1 proteins of rabbit and Tetrahymena thermophila"Biochemistry (Moscow). 64. 1648-1658 (1999)

[文献書誌] Wada, M., Nakamura, Y.: "Type-II major-surface-glycoprotein family of Pneumocystis carinii"J. Euk. Microbiol.. 46. 151S-152S (1999)

[文献書誌] Wada, M., Nakamura, Y.: "Immunological characterization of surface subtilisin-like protease (SSP) of Pneumocystis carinii"J. Euk. Microbiol.. 46. 125S-126S (1999)

[文献書誌] Wada, M., Nakamura, Y.: "Type-II major-surface-glycoprotein family of Pneumocystis carinii under the control of novel expression elements"DNA Res.. 6. 211-217 (1999)

[文献書誌] Tin, O. F., Rykunova, A. L., Muranova, T. A., Toyoda, T., Ito, K., Suzuki, T., Watanabe, K., Garber, M. B., Nakamura, Y.: "Proteolytic fragmentation of polypeptide release factor 1 of Thermus thermophilus and crystallization of the stable fragments"Biochimie, In Press. (2000)

[文献書誌] Ito, K., Uno, M., Nakamura, Y.: "A tripeptide 'anticodon deciphers' stop codons in messenger RNA"Nature. 403. 680-683 (200)

[文献書誌] Abe, H., Abo, T., Aiba, H.: "Regulation of intrinsic terminator by translation in Escherichia coli : transcription termination at a distance downstream"Genes to Cells. 4. 87-97 (1999)

[文献書誌] Tagami, H., Aiba, H.: "An inactive open complex mediated by UP element ant Escherichia coli promoter"Proc. Natl. Acad. Sci. USA. 96. 12914-12919 (1999)

[文献書誌] Tanaka, Y., Kimata, K., Inada, T., Tagami, H., Aiba, H.: "Negative regulation of the pts operon by Mls : Mechanism underlying glucose induction in Escherichia coli"Genes to Cells. 4. 391-399 (1999)

[文献書誌] Sugiyama, A., Noguchi, K., Kitanaka, C., Katou, N., Tashiro, F., Ono, T., Yoshida, M. C., Kuchino, Y.: "Molecular cloning and chromosomal mapping of mouse intronless myc gene acting as a potent apoptosis inducer"Gene. 226. 273-283 (1999)

[文献書誌] Mochizuki, T., Kitanaka, C., Noguchi, K., Muramatsu, T., Asai, A., Kuchino, Y.: "Physical and functional interaction between Pim-1 kinase and Cdc25A phosphatase : implication for the Pim-1-mediated activation of the c-Myc signaling pathway"J. Biol. Chem.. 274. 18659-18666 (1999)

[文献書誌] Noguchi, K., Kitanaka, C., Yamana, H., Kokubu, A., Mochizuki, T., Kuchino, Y.: "Regulation of c-Myc through phosphorylation at Ser-62 and -71 by c-Jun N-terminal kinase"J. Biol. Chem.. 274. 32580-32587 (1999)

[文献書誌] Watanabe, S., Muramatsu, T., Ao, H., Hirayama, Y., Takahashi, K., Tanokura, M., Kuchino, Y.: "Molecular cloning of the Lon protease gene form Thermus thermophilus HB8 and characterization of its gene product"E. J. Biochem.. 266. 811-819 (1999)

[文献書誌] Murakami, Y., Matsufuji, S., Hayashi, S., Tanahashi, N., Tanaka, K.: "ATP-dependent inactivation and sequestration of ornithine decarboxylase by the 26S proteasome is a prerequisite for degradation"Mol. Cell. Biol.. 19. 7216-7227 (1999)

[文献書誌] Suka, M., Matsufuji, S., Murakami, Y.: "Dietary induction of ornithine decarboxylase in male mouse kidney"Biochim. Biophys. Acta.. 1472. 455-461 (1999)

[文献書誌] Saito, T., Hascilowicz, T., Ohkido, I., Kikuchi, Y., Okamoto, H., Hayashi, S., Murakami, Y., Matsufuji, S.: "Two zebrafish antizymes with different expression and activities"Biochem. J.. 345. 99-106 (2000)

[文献書誌] Isoyama, T., Kamoshita, N., Yasui, K., Iwai, A., Shiroki, K., Toyoda, H., Yamada, A., Takasaki, Y., Nomoto, A.: "Lower concentration of La protein required for internal ribosomal entry onhepatitis C virus RNA than on poliovirus RNA"J. Gen. Virol.. 80(9). 2319-2328 (1999)

[文献書誌] Maegawa, S., Yasuda, K., Inoue, K.: "Maternal mRNA localization of zebrafish DAZ-like gene"Mech. Dev.. 81. 223-226 (1999)

[文献書誌] Handa, N., Nureki, O., et al.: "Structural bases for recognition of the tra mRNA precursor by the Sex-lethal protein"Nature. 398. 579-585 (1999)

[文献書誌] Kigawa, T., et al.: "Cell-free production and stable Oisotope labeling of milligram-quantities of proteins"FEBS Lett.. 442. 15-19 (1999)

[文献書誌] Chi, S.-W., et al.: "Chemical shift perturbation studies of the Interactions of the second RNA-binding domain of the Drosophila Sex-lethal protein with the transformer pre-mRNA polyuridine tract and 3' splice site sequences"Eur. J. Biochem.. 260. 649-660 (1999)

[文献書誌] Chi, S., et al.: "Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells"Oncogene. 18. 2281-2290 (1999)

[文献書誌] Horie, N., et al.: "Modified nucleosides in the first positions of the anticodons of tRNALeu4 and tRNALeu5 from Escherichia coli"Biochemistry. 38. 207-217 (1999)

[文献書誌] Atkins, J. F., Bock, A., Matsufuji, S., Gesteland, R. F.: "Dynamics of the Genetic Code"Cold Spring Habor Laboratory Press. 709 (1999)

1999 年度実績報告書

中村義一東京大学, 医科学研究所, 助教授 (40114590)