STRUCTURAL STUDIES OF FUNCTIONAL RNA

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。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 RNA自我剪接I组内含子的发现提供了第一个直接证据，证明并非所有的酶都是蛋白质。 此外，已经发现一组称为核糖开关的RNA可以调节基因表达。 我们实验室的一个重点是确定这些RNA的晶体结构。我们最近报道了晶体结构的几个组I内含子剪接中间体的状态相关的外显子连接反应，现在正在进行结构研究，以表征完整的剪接途径，这个内含子的剪接和后剪接反应的第一步为目标。此外，我们还解决了与其天然配体葡糖胺-6-磷酸结合的GlmS核酶的结构。我们现在正致力于GEMM和甘氨酸核糖开关的第一个结构。甘氨酸核糖开关含有两个适体，其对甘氨酸浓度的变化响应协同性。GEMM核糖开关是参与细胞信号传导的RNA的第一个例子，因为它结合第二信使信号分子，环状双（3 '-5'）二鸟苷酸（c-diGMP）。这个项目的重点是第一组自我剪接内含子沿着与GEMM和甘氨酸核糖开关。

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. The discovery of the RNA self-splicing group I intron provided the first direct evidence that not all enzymes are proteins. Additionally, it has been found that a group of RNAs called riboswitches can regulate gene expression. One focus in our laboratory is the determination of crystal structures of these RNAs. We recently reported crystal structures of several group I intron splicing intermediates in states related to the exon ligation reaction, and are now undertaking structural studies to characterize the complete splicing pathway of this intron by targeting the first step of splicing and post splicing reactions. Additionally, we have also solved the structure of the GlmS ribozyme bound to its native ligand, glucosamine-6-phosphate. We are now working towards the first structures of the GEMM and glycine riboswitches. The glycine riboswitch contains two aptamers that respond cooperativity to changes in glycine concentration. The GEMM riboswitch is the first example of an RNA that is involved in cell signaling, as it binds a second messenger signaling molecule, cyclic bis(3'-5')diguanylic acid (c-diGMP). This project focuses on the group I self-splicing intron along with the GEMM and glycine riboswitches.