Mechanism of RNA function expression

本课题组旨在从RNA的结构出发，阐明其功能的分子机制。它由两个主要小组组成，一个小组研究剪接机制和tRNA结构功能，另一个小组试图建立方法，通过稳定同位素标记rna特异性位点，通过高分辨率核磁共振空间镜分析rna的结构。剪接组首次发现剪接体中的U6sn RNA直接与剪接反应底物mRNA前体结合，具有催化作用。该小组还成功地阐明了果蝇选择性剪接的调控机制，这可能是由参与其中的各种基因产物（如tra和sxl蛋白）与底物mRNA前体中的某些特定序列相互作用引起的。tRNA组专注于动物线粒体（mt） tRNA的结构分析，具有不同寻常的二级结构和不同寻常的遗传密码，更多地阐明tRNA的解码机制。该小组创造了一个新的想法，即即使是不寻常的mt tRNA也可以像其他常见的tRNA一样在核糖体上起作用，其机制是，mt tRNA的两个功能位点（反密码子和CCA端）之间的相互距离和方向可以通过mt tRNA内部特殊的三级相互作用保持恒定。研究小组还发现，mt trna的反密码子第一个字母（有时是第二个字母）上的修饰核苷（如5-甲酰基胞苷、7-甲基鸟苷和假尿嘧啶）通过形成不寻常的密码子-反密码子碱基配对，直接参与解码不寻常的遗传密码。核磁共振组建立了RNA的virto合成方法，在所需的位置上引入稳定的同位素。利用该方法，该小组成功地阐明了i组内含子中鸟嘌呤残基的识别位点以及sx1蛋白与该蛋白识别的短RNA片段的相互作用。对sx1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

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