RNA情報発現系の時空間ネットワーク

2006 Fiscal Year Annual Research Report

• Project/Area Number: 13051101
• Research Institution: The University of Tokyo
• Principal Investigator: 中村 義一 東京大学, 医科学研究所, 教授 (40114590)
• Co-Investigator(Kenkyū-buntansha): 坂本 博 神戸大学, 理学部, 教授 (00187048) ; 塩見 春彦 徳島大学, ゲノム機能研究センター, 教授 (60202107) ; 饗庭 弘二 名古屋大学, 大学院理学研究科, 教授 (20025662) ; 横山 茂之 東京大学, 大学院理学系研究科, 教授 (00159229) ; 松藤 千弥 東京慈恵会医科大学, 医学部, 教授 (50192753)
• Keywords: RNA / ネットワーク / RNA蛋白質複合体 / 高次複合機能 / 分子擬態 / ポストゲノム / 転写後調節 / 翻訳調節

Research Abstract

本領域は総括班と4つの計画研究及び公募研究から構成され、緊密な連携の下に領域全体及び各班の研究目標を達成するように推進された。各研究班の研究成果の概要は以下の通りである。
[総括班]平成18年12月3-7日には2回目となるRNA国際シンポジウムを伊豆で開催。国外から20名の研究者を招聘し約200名が参加登録。平成18年度のノーベル医学生理学賞がRNA干渉の研究に授与されたこともあって盛会となった。又、特定領域研究者のみならず社会とのコミュニケーションを目的として、RNA Network Newsletterの年2回発行を継続し、各方面からの高い評価と愛読を頂戴して全10冊の発行を完了した。RNA若手の会「RNA新大陸のフロンティア達」(平成18年9月11日〜13日、於裾野)開催を支援した。
[A01班・RNPマシーン]RNPマシーンの構造生物学的な研究が進展した。特に、RNAヘリケースであるVasaとRNA、ATPアナログとの三重複合体のX線結晶構造の解明、古細菌におけるシステイン生合成の第一段階として機能するホスホセリルtRNA合成酵素とtRNA^<cys>との複合体の構造解明等、機能構造事例が集積拡張した。さらに、翻訳伸長や終結に要として働くリボソーム蛋白質について精緻な機能研究成果が得られた。
[A02班・RNA制御スイッチ]RNA制御スイッチによる遺伝子発現に関する研究を推進し、特にmRNAサーベイランスや、tRNA機能の構造生物学的裏付けに大きな進展があった。
[A03班・動くRNA]神経特異的RNA結合タンパク質HuDがキャップ構造依存的な翻訳促進機能をもつことを明らかにした。また、線虫クロモドメインタンパク質MRG-1が常染色体のみに局在し、性染色体の遺伝子発現抑制や生殖細胞におけるトランス遺伝子発現抑制に関与することを明らかにした。
[A04班・高次複合系RNA動態]幹細胞形成、生殖細胞形成、神経可塑性、さらには行動等の複雑な生命現象に関与するRNAレベルの遺伝情報発現調節機構(特に翻訳、分解とスプライシング)を明確にした。さらに、複雑な生命の「陰のプログラム」ではないかと予想される各種non-coding RNAの生合成経路とその機能を解明した。

Research Products

• [Journal Article] RNA aptamers targeting the C-terminal of KRAS oncoprotein generated by an improved SELEX with isothermal RNA amplification. (2007)
  • Author(s): Tanaka, Y., Akagi, K., Nakamura, Y., Kozu, T.
  • Journal Title: Oligonucleotides 17 Pages: 12-21
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Human and mouse protein non-coding snoRNA host genes with dissimilar nucleotide sequences show chromosomal synteny. (2007)
  • Author(s): Tanaka-Fujita, R., Soeno, Y., Satoh, H., Nakamura, Y., Mori, S.
  • Journal Title: RNA (In Press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A Systematic Evaluation of the Function of the Protein-Remodeling Factor Hsp104 in [PSI+] Prion Propagation in S. cerevisiae by Comprehensive Chromosomal Mutations. (2007)
  • Author(s): Takahashi, A., Hara, H., Kurahashi, H., Nakamura,Y.
  • Journal Title: Prion (In Press)
• [Journal Article] Translation termination, the prion [PSI^+], and ribosome recycling. In : Sonenberg N, Hershey JWB, Mathews MB, eds. Translational Control in Biology and Medicine. (2007)
  • Author(s): Ehrenberg, M., Hauryliuk V., Crist C.G., Nakamura, Y.
  • Journal Title: Cold Spring Harbor, pp. (New York : Cold Spring Harbor Laboratory Press) Pages: 173-196
• [Journal Article] Reduced action of polypeptide release factors induces mRNA cleavage and tmRNA tagging at stop codons in Escherichia coli. (2007)
  • Author(s): Li, X., Yokota, T., Ito, K., Nakamura, Y., Aiba, H.
  • Journal Title: Mol. Micro. 63 Pages: 116-126
• [Journal Article] Channel mutations in Hsp 104 hexamer distinctively affect thermotolerance and prion-specific propagation. (2007)
  • Author(s): Kurahashi, H., Nakamura, Y.
  • Journal Title: Mol. Microbiol. 63 Pages: 1669-1683
• [Journal Article] The role of N-terminal domain of translational release factor eRF3 for the control of functionality and stability in S. cerevisiae. (2007)
  • Author(s): Kodama, H., Ito, K., Nakamura, Y.
  • Journal Title: Genes Cells (In Press)
• [Journal Article] 翻訳研究のダイナミズム (2007)
  • Author(s): 中村義一
  • Journal Title: 翻訳制御(実験医学)(中村義一 監修) 25 Pages: 2-4
• [Journal Article] MRG-1, an autosome-associated protein, silences X-linked genes and protects germline immortality in Caenorhabditis elegans. (2007)
  • Author(s): Takasaki T., Liu, Z., Habara, Y., Nishiwaki, K., Nakayama, J., Inoue, K., Sakamoto, H., Strome, S.
  • Journal Title: Development 134 Pages: 757-767
• [Journal Article] Spatiotemporal localization of germ plasm RNAs during zebrafish oogenesis. (2007)
  • Author(s): Kosaka, K., Kawakami, K., Sakamoto, H., Inoue, K.
  • Journal Title: Mech. Dev. 124 Pages: 279-289
• [Journal Article] A Slicer-mediated mechanism for rasiRNA 5'end formation in Drosophila. (2007)
  • Author(s): Gunawardane, LS., Saito, K., Nishida, KM., Miyoshi, K., Kawamura, Y., Nagami, T., Siomi, H., Siomi, MC.
  • Journal Title: Science 315 Pages: 1587-1590
• [Journal Article] Expanding RNA physiology : microRNAs in a unicellular organism. (2007)
  • Author(s): Siomi, H., Siomi, MC.
  • Journal Title: Genes ＆ Development (In press)
• [Journal Article] In vitro RNA cleavage assay for Argonaute-family proteins. (2007)
  • Author(s): Miyoshi, K., Uejima, H., Nagami, T., Siomi, H., Siomi, MC.
  • Journal Title: Methods in Mol Biol. (In press)
• [Journal Article] Reduced action of polypeptide release factors induces mRNA cleavage and tmRNA tagging at stop codons in Escherichia coli. (2007)
  • Author(s): Li, X., Teruaki Yokota, T., Ito K., Nakamura Y., Aiba, H.
  • Journal Title: Mol. Microbiol. 63 Pages: 116-126
• [Journal Article] The crystal structure of leucyl/phenylalanyl-tRNA-protein transferase from Escherichia coli. (2007)
  • Author(s): Dong, X., Kato-Murayama, M., Muramatsu, T., Mori, H., Shirouzu, M., Bessho, Y., Yokoyama, S.
  • Journal Title: Protein Sci. 16 Pages: 528-534
• [Journal Article] A snapshot of the 30S ribosomal subunit capturing mRNA via the Shine-Dalgarno interaction. (2007)
  • Author(s): Kaminishi, T., Wilson, D.N., Takemoto, C., Harms, J.M., Kawazoe, M., Schluenzen, F., Hanawa-Suetsugu, K., Shirouzu, M., Fucini, P., Yokoyama, S.
  • Journal Title: Structure 15 Pages: 289-297
• [Journal Article] Structural basis for interaction of the ribosome with the switch regions of GTP-bound elongation factors. (2007)
  • Author(s): Connell, S.R., Takemoto, C., Wilson, D.N., Wang, H., Murayama, K., Terada, T., Shirouzu, M., Rost, M., Schuler, M., Jan, G., Marylena, D., Mielke, T., Fucini, P., Yokoyama, S., Spahn, C.M.T.
  • Journal Title: Mol. Cell 25 Pages: 751-764
• [Journal Article] Structural insights into the first step of RNA-dependent cysteine biosynthesis in archaea. (2007)
  • Author(s): Fukunaga, R., Yokoyama, S.
  • Journal Title: Nat. Struct. Mol. Biol. 14 Pages: 272-279
• [Journal Article] Role of modified nucleosides in the translation function of tRNAs from extreme thermophilic bacteria and animal mitochondria. (2007)
  • Author(s): K.Watanabe
  • Journal Title: Bulletin of the Chemical Society of Japan. (In press)
• [Journal Article] Ribosomal protein L11 mutations in two functional domains equally affect release factor 1 and 2 activity. (2006)
  • Author(s): Sato, H., Ito, K., Nakamura, Y.
  • Journal Title: Mol. Microbiol. 60 Pages: 108-120
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Conformation preserved in a weak-to-strong or strong-to-weak [PSI^+] conversion during transmission to Sup35 prion variants. (2006)
  • Author(s): Crist, C.G., Kurahashi, H., Nakayashiki, T., Nakamura,Y.
  • Journal Title: Biochimie 88 Pages: 485-496
• [Journal Article] RNA aptamers to mammalian initiation factor 4G inhibit cap-dependent translation by blocking the formation of initiation factor complexes. (2006)
  • Author(s): Miyakawa, S., Oguro, A., Ohtsu, T., Imataka, H., Sonenberg, N., Nakamura,Y.
  • Journal Title: RNA 12 Pages: 1825-1834
• [Journal Article] Selection of RNA aptamers against recombinant transforming growth factor-beta type III receptor displayed on cell surface. (2006)
  • Author(s): Ohuchi, S.P., Ohtsu, T., Nakamura, Y.
  • Journal Title: Biochimie 88 Pages: 897-904
• [Journal Article] Cross-talk between RNA and prions. (2006)
  • Author(s): Crist, G.C., Nakamura, Y.
  • Journal Title: J. Biochem. (Tokyo) 140 Pages: 167-173
• [Journal Article] RNA科学概論 (2006)
  • Author(s): 中村義一
  • Journal Title: 遺伝子医学MOOK「RNAと創薬」(中村義一 監修)(メディカルドゥ) Pages: 23-30
• [Journal Article] RNA抗体としてのポテンシャル (2006)
  • Author(s): 中村義一
  • Journal Title: 遺伝子医学MOOK「RNAと創薬」(中村義一 監修)(メディカルドゥ) Pages: 39-46
• [Journal Article] アプタマー工学 (2006)
  • Author(s): 大内将司
  • Journal Title: 遺伝子医学MOOK「RNAと創薬」(中村義一 監修)(メディカルドゥ) Pages: 32-38
• [Journal Article] リボザイム・テクノロジー (2006)
  • Author(s): 大内将司
  • Journal Title: 遺伝子医学MOOK「RNAと創薬」(中村義一 監修)(メディカルドゥ) Pages: 143-151
• [Journal Article] 翻訳開始因子 (elF) の異常による癌化と創薬 (2006)
  • Author(s): 望月潔隆, 小黒明広, 中村義一
  • Journal Title: 遺伝子医学MOOK「RNAと創薬」(中村義一 監修)(メディカルドゥ) Pages: 195-201
• [Journal Article] 構造体として機能するRNA (2006)
  • Author(s): 大内将司
  • Journal Title: 実験医学 24 Pages: 800-804
• [Journal Article] RNAは擬態する (2006)
  • Author(s): 中村義一
  • Journal Title: 科学 76 Pages: 500-506
• [Journal Article] アプタマー医薬品 (2006)
  • Author(s): 藤原将寿, 宮川伸, 中村義一
  • Journal Title: BIO Clinica 21 Pages: 725-729
• [Journal Article] 核酸創薬 (2006)
  • Author(s): 藤原将寿, 宮川伸, 中村義一
  • Journal Title: バイオテクノロジージャーナル 6 Pages: 650-654
• [Journal Article] RNAルネッサンスー遺伝子新革命 (2006)
  • Author(s): 田原総一朗, 中村義一
  • Journal Title: 医薬経済社
• [Journal Article] アプタマー創薬 (2006)
  • Author(s): 藤原将寿, 宮川伸, 中村義一
  • Journal Title: ファルマシア 42 Pages: 1232-1236
• [Journal Article] 「RNAと疾患」監修序文 (2006)
  • Author(s): 中村義一, 大内将司
  • Journal Title: 分子細胞治療 5 Pages: 391-392
• [Journal Article] 酵母においてプリオン説は証明された (2006)
  • Author(s): 倉橋洋史, 中村義一
  • Journal Title: 科学 76 Pages: 1128-1133
• [Journal Article] 「RNAと生命」編集序文 (2006)
  • Author(s): 中村義一
  • Journal Title: 蛋白質核酸酵素 51 Pages: 2405-2406
• [Journal Article] 桧舞台に躍り出たRNA (2006)
  • Author(s): 中村義一
  • Journal Title: 「RNAと生命」(蛋白質核酸酵素)(中村義一編集) 51 Pages: 2409-2412
• [Journal Article] アプタマー医薬 (2006)
  • Author(s): 宮川伸, 藤原将寿, 中村義一
  • Journal Title: 「RNAと生命」(蛋白質核酸酵素)(中村義一編集) 51 Pages: 2521-2527
• [Journal Article] 翻訳終結因子とプリオン (2006)
  • Author(s): 中村義一
  • Journal Title: 「RNAと生命」(蛋白質核酸酵素)(中村義一編集) 51 Pages: 2574-2582
• [Journal Article] Differential regulation of germline specific mRNAs in soma and primordial germ cells by zebrafish miR-430. (2006)
  • Author(s): Mishima, Y., Giraldez, A.J., Takeda, Y., Fujiwara, T., Sakamoto, H., Schier, A.F., Inoue, K.
  • Journal Title: Current Biology 16 Pages: 12135-21142
• [Journal Article] Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. (2006)
  • Author(s): Saito, K., Nishida, KM., Mori, T., Kawamura, Y., Miyoshi, K., Nagami, T., Siomi, H., Siomi, MC.
  • Journal Title: Genes ＆ Development 20 Pages: 2214-2222
• [Journal Article] In vitro pre-miRNA processing assays using Drosophila S2 cell lysates. (2006)
  • Author(s): Ishizuka, A., Saito, K., Siomi, MC., Siomi, H.
  • Journal Title: Methods in Mol Biol. 342 Pages: 277-286
• [Journal Article] Protein tagging at rare codons is caused by tmRNA action at the 3'end of nonstop mRNA generated in response to ribosome stalling. (2006)
  • Author(s): Li, X., Hirano, R., Tagami, H., Aiba, H.
  • Journal Title: RNA 12 Pages: 248-255
• [Journal Article] Translational repression is sufficient for gene silencing by bacterial small non-coding RNAs in the absence of mRNA destruction. (2006)
  • Author(s): Morita, T., Mochizuki, Y., Aiba, H.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 103 Pages: 4858-4863
• [Journal Article] Yeel, a novel protein involved in modulation of the activity of the glucose-phosphotransferase system in Escherichia coli K-12. (2006)
  • Author(s): Becker.A.K., Zeppenfeld, T., Staab, A., Seitz, S., Boos, W., Morita T., Aiba H., Mahr.K., Titgemeyer.F., Jahreis.K.
  • Journal Title: J Bacteriol. 188 Pages: 5439-5449
• [Journal Article] Base-pairing requirement for RNA silencing by a bacterial small RNA and acceleration of duplex formation by Hfq. (2006)
  • Author(s): Kawamoto, H., Koide Y., Morita, T., Aiba, H
  • Journal Title: Mol. Microbiol. 61 Pages: 1013-1022
• [Journal Article] Structural basis for substrate recognition by the editing domain of isoleucyl-tRNA synthetase. (2006)
  • Author(s): Fukunaga, R., Yokoyama, S.
  • Journal Title: J. Mol. Biol. 359 Pages: 901-912
• [Journal Article] Structural basis of the water-assisted asparagine recognition by asparaginyl-tRNA synthetase. (2006)
  • Author(s): Iwasaki, W., Sekine, S., Kuroishi, C., Kuramitsu, S., Shirouzu, M., Yokoyama, S.
  • Journal Title: J. Mol. Biol. 360 Pages: 329-342
• [Journal Article] Crystal structure of the tRNA pseudouridine synthase TruA from Thermus thermophilus HB8. (2006)
  • Author(s): Dong, X., Bessho, Y., Shibata, R., Nishimoto, M., Shirouzu, M., Kuramitsu, S., Yokoyama, S.
  • Journal Title: RNA Biology 3 Pages: 115-121
• [Journal Article] The antibiotic kasugamycin mimics mRNA nucleotides to destabilize tRNA binding and inhibit canonical translation initiation. (2006)
  • Author(s): Schluenzen, F., Takemoto, C., Wilson, D.N., Kaminishi, T., Harms, J., Hanawa-Suetsugu, K., Szaflarski, W., Kawazoe, M., Shirouzu, M., Nierhaus, H.K., Yokoyama, S., Fucini, P.
  • Journal Title: Nat. Struct. Mol. Biol. 13 Pages: 871-878
• [Journal Article] Structural and mutational studies of the amino acid-editing domain from archaeal/eukaryal phenylalanyl-tRNA synthetase. (2006)
  • Author(s): Sasaki, H.M., Sekine, S., Sengoku, T., Fukunaga, R., Hattori, M., Utsunomiya, Y., Kuroishi, C., Kuramitsu, S., Shirouzu, M., Yokoyama, S.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 103 Pages: 14744-14749
• [Journal Article] The crystal structure of mouse Nup35 reveals atypical RNP motifs an novel homodimerization of the RRM domain. (2006)
  • Author(s): Handa, N., Kukimoto, M., Akasaka, R., Kishishita, S., Murayama, K., Terada, T., Inoue, M., Kigawa, T., Kose, S., Imamoto, N., Tanaka, A., Hayashizaki, Y., Shirouzu, M., Yokoyama, S.
  • Journal Title: J. Mol. Biol. 363 Pages: 114-124
• [Journal Article] Solution structures of the SURP domains and the subunit-assembly mechanism within the splicing factor SF3a complex in 17S U2 snRNP. (2006)
  • Author(s): Kuwasako, K., He, F., Inoue, M., Tanaka, A., Sugano, S., Guntert, P., Muto, Y., Yokoyama, S.
  • Journal Title: Structure 14 Pages: 1677-1689
• [Journal Article] Structural bases of transfer RNA-dependent amino-acid recognition and activation by glutamyl-tRNA synthetase. (2006)
  • Author(s): Sekine, S., Shichiri, M., Bernier, S., Chenvert, R., Lapointe, J., Yokoyama, S.
  • Journal Title: Structure 14(12) Pages: 1791-1799
• [Journal Article] Temperature-dependent biosynthesis of 2-thioribothymidine of Thermus thermophilus tRNA. (2006)
  • Author(s): N.Shigi, T.Suzuki, T.Terada, M.Shirouzu, S.Yokoyama, K.Watanabe.
  • Journal Title: J. Biol. Chem. 281 Pages: 2104-2113
• [Journal Article] Identification of two tRNA thiolation genes required for cell growth at extremely high temperatures. (2006)
  • Author(s): N.Shigi, Y.Sakaguchi, T.Suzuki, K.Watanabe
  • Journal Title: J. Biol. Chem. 281 Pages: 14296-14306
• [Journal Article] A protein extension to shorten RNA : elongated elongation factor-Tu recognizes the D-arm of T-armless tRNAs in nematode mitochondria. (2006)
  • Author(s): M.Sakurai, Y.Watanabe, K.Watanabe, T.Ohtsuki
  • Journal Title: Biochemical J. 45 Pages: 10920-10927
• [Journal Article] Identification of the residues involved in the unique serine specificity of Caenorhabditis elegans mitochondrial EF-Tu2. (2006)
  • Author(s): A.Sato, Y.Watanabe, T.Suzuki, M.Komiyama, K.Watanabe, T.Ohtsuki.
  • Journal Title: Biochemistry 45 Pages: 10920-10927
• [Journal Article] Characterization of a counterpart to mammalian ornithine decarboxylase antizyme in prokaryotes. (2006)
  • Author(s): Yamaguchi, Y., Takatsuka, Y., Matsufuji, S., Murakami, Y., Kamio, Y.
  • Journal Title: J. Biol. Chem. 281 Pages: 3995-4001
• [Journal Article] The C-terminal domain of the archaeal leucyl-tRNA synthetase prevents misediting of isoleucyl-tRNAIle.
  • Author(s): Fukunaga, R., Yokoyama, S.
  • Journal Title: Biochemistry (In press)
• [Journal Article] Structural basis for functional mimicry of long-variable-arm tRNA by tmRNA.
  • Author(s): Bessho, Y., Shibata, R., Sekine, S., Murayama, K., Higashijima, K., Hori-Takemoto, C., Shirouzu, M., Kuramitsu S., Yokoyama, S.
  • Journal Title: Proc. Natl. Acad. Sci. USA. (In press)