Molecular Basis for RNA Dynamic Function

本课题旨在通过揭示RNA的催化功能和信息表达的高级调控功能的分子机制，以及寻找和人工合成催化新反应的核酶，将RNA的动态功能系统化，从而建立RNA动态功能在生命现象中的分子基础。在这些研究成果的基础上，我们将探索诸如发育、分化和疾病等高层次生命现象的分子机制，并阐明许多未知的RNA功能。与此同时，新的RNA动态功能分析方法也将被开发出来。为此目的，在一个主小组下组织了三个研究小组和一个特别小组。首先，“RNA动态功能”组成功地确定了具有剪接功能的I组内含子的最小功能区域，构建了具有序列识别和RNA切割活性的二聚体锤头核酶（maxiz…More yme），并在细胞中表达了maxizyme与解旋酶的复合物。第二，“RNA信息功能”组获得了“翻译因子发现tRNA分子模仿”这一备受赞赏的成果，从而阐明了翻译反应的基本原理。在蛋白质对RNA识别机制的研究中，通过对sxl蛋白与单链RNA复合物的NMR分析和对氨基酰基-tRNA合成酶与tRNA复合物的x射线分析，成功地阐明了蛋白质对RNA的分子识别机制。第三，“RNA高级功能”成功构建了线粒体基因导入小鼠，有助于阐明疾病原因和衰老机制。发现线粒体疾病是由于线粒体trna反密码子第一位置的牛磺酸修饰缺失引起的。tmRNA的功能结构也得到了成功的解析。该研究项目进展顺利，估计已实现约75%的原定目标。在日本RNA协会研究项目的进展过程中，在该项目的基础上建立了一个支持日本RNA研究的支持系统。少

The aim of this research project is to establish the molecular basis of RNA dynamic functions in the phenomena of life by systematizing the RNA dynamic functions through revealing the molecular mechanisms of catalytic functions of RNA and high-level control functions of information expression, and searching and artificially producing ribozymes catalyzing new reaetions. On the basis of the results obtained by these researches, molecular mechanisms of high-level phenomena of life such as development, differentiation and disease will be pursued and many unknown RNA functions will be elucidated. In parallel with these achievements new methods for analyzing RNA dynamic functions will be developed. For this purpose three research groups and one special team were organized under a master group. The first, 「RNA dynamic functions」 group succeeded in determination of a minimal functional region of group I intron possessing the splicing function, construction of dimeric hammerhead ribozyme (maxiz … More yme) providing both sequence recognition and RNA scission activities, and expression of the complex of the maxizyme with a helicase in cells. The second, 「RNA information fuctions」group obtained a highly appreciated result of discovery of tRNA molecular mimicry by translation factors」 which leads to elucidating the basic principle of the translation reaction. In research for RNA recognition mechanisms by proteins, NMR analysis of a complex of sxl protein with a single-stranded RNA and X-ray analysis of a complex of aminoacyl-tRNA synthetase with tRNA succeeded in elucidating molecular recognition mechanisms of RNA by proteins. The third, 「RNA high-level functions」 succeeded in constructing a mitochondrial gene-introduced mouse useful for elucidating the cause of disease and mechanism of senescence. It was found that mitochondrial diseases are caused by lacking in the taurine-modification at the anticodon first position of mitochondrial tRNAs. The elucidation of functional structures of tmRNA was also successful. The research project has been progressing well and it is estimated that about 75% of the original aims have been achieved. During progress in the research project Japan RNA Society, a supporting system for supporting the RNA research in Japan was established on the basis of the project. Less