STRUCTURAL STUDIES OF FUNCTIONAL RNA

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 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。甘氨酸核糖开关包含两个适体，它们对甘氨酸浓度的变化产生协同反应。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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.