The molecular basis of the higher function of RNA molecules

RNA分子高级功能的分子基础

• 批准号: 09278104
• 负责人: OHTA Shigeo
• 金额: $ 123.39万
• 依托单位: Institute of Gerontology, Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas (A)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09278104/
• 关键词: mitochondrial disease; post-translational modification; germ-line cells; meiosis; tmRNA; tRNA; 高次機能; RNA; tmRNA; 古細菌; tRNA; 遺伝子変異; 発生; 分化; ミトコンドリア; mtRNA; ミトコンドリア脳筋症; trans-translction

In our group, we have focused interest on the following subjects ; (1)The molecular mechanism on the role of RNA molecules involved in diseases. (2)The molecular mechanism on the roles of RNA molecules involved in development and differentiation. (3)Functional analysis of RNA molecules with a unknown function.Ohta and Watanabe K. purified several mutant mitochondrial tRNA molecules and determined their structure, where the mutant tRNAs are responsible for mitochondrial diseases. We found that some mutant tRNAs lack modification of nucleotides at the third letter of anticodon and that the modification defect reduced the interaction of tRNA and mRNA, leading the unusual protein synthesis as the cause of the diseases.Kobayashi found that mitochondrial rRNAs are required for development of cells responsible for the germ-line, and that the rRNA molecules remove out of mitochondria and turn into components of polysome in the cytosole.Watanabe Y. revealed function of an essential RNA molecule, Mei RNA, for meiosis. Mei RNA binds to a component, which is essential for meiosis, to retain it in the nucleus.Muto identified the structure of tmRNA which plays dual function of tRNA and mRNA.

在我们的小组中，我们的兴趣集中在以下科目上；(1) RNA分子参与疾病的分子机制。(2) RNA分子参与发育分化的分子机制。(3)未知功能RNA分子的功能分析。Ohta和Watanabe K.纯化了几个突变的线粒体tRNA分子并确定了它们的结构，其中突变的tRNA与线粒体疾病有关。我们发现一些突变的tRNA缺乏反密码子第三个字母的核苷酸修饰，这种修饰缺陷减少了tRNA和mRNA的相互作用，导致异常的蛋白质合成成为疾病的原因。Kobayashi发现，线粒体rRNA是负责种系的细胞发育所必需的，rRNA分子从线粒体中移除，变成细胞质中多聚体的组成部分。Watanabe Y.揭示了一种重要的RNA分子Mei RNA在减数分裂中的作用。Mei RNA与减数分裂所必需的成分结合，将其保留在细胞核中。Muto鉴定出具有tRNA和mRNA双重功能的tmRNA结构。

项目成果

Shinozaki-Yabana,S.,Watanabe,Y.,and Yamamoto,M.: "Novel WD-repeat protein Miplp facilitates function of the meiotic regulator Mei2p in fission yeast."Mol.Cell.Biol.. 20巻. 1234-1242 (2000)

Shinozaki-Yabana, S.、Watanabe, Y. 和 Yamamoto, M.：“新型 WD 重复蛋白 Miplp 促进裂殖酵母中减数分裂调节因子 Mei2p 的功能。”Mol.Cell.Biol.. vol. 20. 1234- 1242 (2000)

Felden B., Muto A. et al.: "Presence and location of modified nucleotides in Escherichia coli tmRNA : structural mimicry with tRNA acceptor brances." EMBO J.17. 3188-3196. (1998)

Felden B.、Muto A. 等人：“大肠杆菌 tmRNA 中修饰核苷酸的存在和位置：与 tRNA 受体分支的结构模拟。”

Nameki N. Felden B. Atkins JF. Gesteland RF. Himeno H. Muto A: "Functional and structural analysis of a pseudoknot upstream of the tag-encoded sequence in E. coli tmRNA."J. Mol. Biol.. 286(3). 733-744 (1999)

Nameki N. Felden B. Atkins JF.

Nitta I., Watanabe K. et al.: "Reconstitution of peptide bond formation with Escherichia coli 23S ribosomal RNAdomains." Science. 281. 666-669. (1998)

Nitta I.、Watanabe K. 等人：“用大肠杆菌 23S 核糖体 RNA 结构域重建肽键形成。”

Yamashita A., Watanabe Y. et al.: "RNA-assisted nuclear transport of the meiotic regulator Mei2p in fission yeast." Cell.95. 115-123. (1998)

Yamashita A.、Watanabe Y. 等人：“裂殖酵母中减数分裂调节因子 Mei2p 的 RNA 辅助核运输。”