RNA機能の発現機構

• 研究課題/領域番号: 04272102
• 研究種目: 重点領域研究
• 配分区分: 補助金
• 研究機関: 東京大学
• 研究代表者: 渡辺 公綱 東京大学, 大学院・工学系研究科, 教授 (00134502)
• 研究分担者: 大野 睦人 (大野 陸人) 京都大学, 大学院・理学研究科, 助手 (80201979) ; 西川 一八 (西村 一八) 岐阜大学, 工学部, 教授 (60109262) ; 井上 丹 京都大学, 大学院・理学研究科, 教授 (40114855) ; 志村 令郎 生物分子工学研究所, 所長 (60025426) ; 横山 茂之 東京大学, 大学院・理学系研究科, 教授 (00159229) ; 武藤 裕 東京大学, 理学部, 助手 (30192769) ; 坂本 博 神戸大学, 理学部, 助教授 (00187048)
• 研究期間 (年度): 1992 – 1995
• 研究課題ステータス: 完了 (1996年度)
• 配分額: 227,000千円 (直接経費: 227,000千円); 1995年度: 59,800千円 (直接経費: 59,800千円); 1994年度: 61,700千円 (直接経費: 61,700千円); 1993年度: 56,000千円 (直接経費: 56,000千円); 1992年度: 49,500千円 (直接経費: 49,500千円)
• キーワード: スプライシング / オルタナテイブスプライシング / tRNA / 修飾ヌクレオシド / 塩基対合 / 安定同位体標識 / NMR / 蛋白質 / RNA / 機能構造 / nRNAスプライシング / リボザイム / ミトコンドリア / RNA結合蛋白質 / rRNA / mRNAスプライシング / ミトコンドリアtRNA

研究概要

本研究班は構造を視点としたRNA機能の発現機構の解明を目的として研究を進めてきた。その内容は2つに大別され、一方はスプライシングとtRNAを主たるターゲットとしてそれらの機能発現機構と機能構造を研究するグループと、他方はRNAの機能構造を主として高分解能NMRにより解析するための方法論を確立するグループである。スプライシンググループではスプライソゾーム中で触媒活性を担うと考えられているU6snRNAと基質であるmRNA前駆体との直接的な相互作用を世界で初めて検出し、ショウジョウバエにおけるオルタナテイブスプライシングの制御機構を、それに関わる種々の遺伝子産物(tra、sxl蛋白質など)とmRNA前駆体の特殊配列との相互作用として捉えることに成功した。tRNAグループは主として異常な二次構造を持つ動物ミトコンドリアの立体構造解析と非普遍暗号解読機構の解明を集中して行った。前者ではtRNA分子内部の3次的な相互作用により、片方の腕を欠いた異常tRNAでもアンチコドンとCCA末端という2つの機能部位の相対配置を一定に保つ機構が働いて、リボソーム上で他の正常なtRNAと同等に機能するという新しい概念を創出した。後者では非普遍暗号解読に関わるtRNAの特にアンチコドン領域を解析し、アンチコドン1字目(及び時には2字目)の修飾ヌクレオシド(5-ホルミルシチジン、7-メチルグアノシン、プソイドウリジンなど)が新規塩基対合に密接に関わることを明らかにした。NMRグループは任意の箇所に安定同位体標識を導入した望みの塩基配列をもつRNAの人工合成法を確立した。それを利用してグループIイントロンの基質認識部位や、sxl蛋白質とこれが認識する短鎖配列のRNAとの相互作用の解析に成功した。またsxl蛋白質自身のNMRによる詳細な構造解析から、RNA鎖との結合に必要なアミノ酸部位の特性を明らかにした。

研究成果

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  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(欧文)」より
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  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] T.Suzuki, T.Ueda and K.Watanebe: "A New Method for Identifying the Amino Acid Attached to a Particular RNA in the Cell." FEBS Letters. 381. 195-198 (1996)
  • 説明: 「研究成果報告書概要(欧文)」より
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  • 説明: 「研究成果報告書概要(欧文)」より
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