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Mechanism of RNA function expression

RNA功能表达机制

基本信息

批准号：
04272102
负责人：
WATANABE Kimitsuna
金额：
$ 145.28万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04272102/
关键词：
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

项目摘要

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 sequencesin the substrate mRNA precursors. The tRNA group has concentrated on the structural analysis of animal mitochondrial (mt) tRNAs with unusual secondary structures and o … More 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

本研究组的目标是根据RNA的结构阐明其功能的分子机制。它由两个主要小组组成，一个研究剪接机制和tRNA结构-功能，另一个试图建立方法学，使RNA的结构分析，通过高分辨率NMR spectroscopy通过标记RNA的位点特异性与稳定的同位素。剪接组首次发现剪接体中被认为具有催化功能的U6 snRNA直接与剪接反应的底物mRNA前体结合。本课题组还成功地阐明了果蝇选择性剪接的调控机制，即参与选择性剪接的各种基因产物（如tra和sxl蛋白）与底物mRNA前体中的某些特定序列相互作用而产生的。tRNA研究组主要致力于动物线粒体（mt）tRNA的结构分析，这些tRNA具有不寻常的二级结构， ...更多信息阐明tRNA对不寻常遗传密码的解码机制。该小组创造了一个新的想法，即使是不寻常的mt tRNA也可以像其他常见的tRNA一样在核糖体上发挥作用，其机制是tRNA的两个功能位点（反密码子和CCA末端）之间的相互距离和方向可以通过mt tRNA内的特殊三级相互作用保持恒定。该小组还发现，在mt tRNA的反密码子第一个字母（有时是第二个字母）中的修饰核苷（如5-甲酰胞苷，7-甲基鸟苷和假尿苷）通过形成不寻常的密码子-反密码子碱基配对直接参与不寻常遗传密码的解码。NMR小组建立了RNA的体外合成方法，将稳定同位素引入所需的位置。利用该方法，研究组成功地阐明了I组内含子中鸟嘌呤残基的识别位点以及sx 1蛋白与该蛋白识别的短RNA片段的相互作用。还对sx 1蛋白本身进行了详细的结构分析，从而阐明了参与RNA识别的氨基酸残基的特征。少