Project/Area Number |
04272102
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Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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Allocation Type | Single-year Grants |
Research Institution | The University of Tokyo |
Principal Investigator |
WATANABE Kimitsuna University of Tokyo, Graduate School of Engineering, Professor, 大学院・工学系研究科, 教授 (00134502)
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Co-Investigator(Kenkyū-buntansha) |
OHNO Mutsuhito Kyoto University, Graduate School of Science, Research Associate, 大学院・理学研究科, 助手 (80201979)
NISHIKAWA Kazuya Gifu University, Faculty of Engineering, Professor, 工学部, 教授 (60109262)
INOUE Tan Kyoto University, Graduate School of Science, Professor, 大学院・理学研究科, 教授 (40114855)
SHIMURA Yoshiro Biomolecular Engineering Research Institute, Director, 所長 (60025426)
YOKOYAMA Shigeyuki University of Tokyo, Graduate School of Science, Professor, 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)
|
Project Period (FY) |
1992 – 1995
|
Project Status |
Completed (Fiscal Year 1996)
|
Budget Amount *help |
¥227,000,000 (Direct Cost: ¥227,000,000)
Fiscal Year 1995: ¥59,800,000 (Direct Cost: ¥59,800,000)
Fiscal Year 1994: ¥61,700,000 (Direct Cost: ¥61,700,000)
Fiscal Year 1993: ¥56,000,000 (Direct Cost: ¥56,000,000)
Fiscal Year 1992: ¥49,500,000 (Direct Cost: ¥49,500,000)
|
Keywords | splicing / alternative splicing / tRNA / modified nucleoside / base pairing / stable isotope labeling / NMR / sx1 protein / 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 |
Research Abstract |
This research group aims to elucidate the molecular mechanisms of RNA functions on the basis of their structures. It consists of two main groups, onestudying splicing mechanism and tRNA structure-functions, and another trying to establish methodology to enable structural analysis of RNAs by high-resolution NMR spactroscopy through labeling of RNAs site-specifically with stable isotopes. The splicing group has first found that U6sn RNA in spliceosomewhich is thought to be responsible for catalytic function, directly binds to mRNA precursor, the substrate for splicing reaction. The group also succeeded in elucidating regulation mechanism of the alternative splicing in Drosophila, which can be brought about by interactions between various gene products involved in it (such as tra and sxl proteins) and some specific sequences in the substrate mRNA precursors. The tRNA group has concentrated on the structural analysis of animal mitochondrial (mt) tRNAs with unusual secondary structures and o
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n elucidating decoding mechanisms of tRNAs towards unusual genetic code. The group created a new idea that even unusual mt tRNAs can function on the ribosome as other usual tRNAs by a mechanism that the mutual distance and orientation between two functional sites of tRNA,the anticodon and the CCA end, can be preserved constant by special tertiary interactions within the mt tRNAs. The group also found that modified nucleosides in the anticodon first letter (or sometimes second letter) of mt tRNAs (such as 5-formylcytidine, 7-methylguanosine and pseudouridine) are directly involved in decoding of the unusual genetic code, by forming unusual codon-anticodon basepairings. The NMR group established the in virto synthesis method of RNA into the desired positions of which stable isotopes are introduced. By utilizing the method, the group succeeded in elucidating the recognition sites of guanine residue in groupI intron and the interaction of sx1 protein with a short RNA fragment which is recognized by the protein. The detailed structural analysis of the sx1 protein, itself was also carried out, which lead to elucidation of characteristic feature of amino acids residues involved in recognition of the RNA. Less
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