STRUCTURES OF RIBOSOME-BOUND MODIFIED TRNAS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 为子项目列出的总成本可能 代表子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 核酸的结构-功能关系，如蛋白质合成中tRNA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RNA作为潜在靶标或工具的结构-功能关系，我们已经开发了用于引入天然的、非天然的和稳定的同位素标记的核苷的方法。我们已经发现，在tRNA修饰核苷发挥重要的结构和功能的作用，无论是在tRNA分子内，并在tRNA反密码子识别的选择密码子在摆动位置。修饰的核苷改变密码子“摆动”，增强核糖体结合，解释程序性翻译移码，是氨酰-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类tRNA以引发逆转录。

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.