STRUCTURES OF RIBOSOME-BOUND MODIFIED TRNAS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 核酸的结构-功能关系，如tRNA在蛋白质合成中的结构-功能关系，是所有细胞和分子生物学的基础。为了探索作为潜在靶点或工具的RNA的结构-功能关系，我们开发了引入天然、非天然和稳定的同位素标记核苷的方法。我们发现，tRNA中的修饰核苷在tRNA分子内和在摆动位置选择密码子的tRNA反密码子识别中都发挥着重要的结构和功能作用。修饰的核苷改变密码子“摆动”，增强核糖体结合，解释程序化的翻译框架转移，是氨基酰-tRNA合成酶识别的决定因素，并参与人类免疫缺陷病毒选择特定的人tRNA以启动逆转录。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Structure-function relationships of nucleic acids, such as that of tRNA in protein synthesis, are fundamental to all cell and molecular biology. In order to probe the structure-function relationships of RNAs as potential targets or tools, we have developed methods for the introduction of native, non-natural, and stable isotope labeled nucleosides. We have found that modified nucleosides in tRNA play an important structural and functional role both within the tRNA molecules and in tRNA anticodon recognition of select codons at the wobble position. Modified nucleosides alter codon "wobble", enhance ribosome binding, explain programmed translational frameshifting, are determinants for aminoacyl-tRNA synthetase recognition, and are involved in human immunodeficiency virus selection of a specific human tRNA to prime reverse transcription.