STRUCTURAL STUDIES OF FUNCTIONAL RNA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 RNA自剪接第一组内含子的发现提供了第一个直接证据，证明并不是所有的酶都是蛋白质。此外，人们还发现，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。我们最近报道了几个与外显子连接反应相关状态的I类内含子剪接中间体的晶体结构，并正在进行结构研究，通过剪接反应的第一步和剪接后反应来表征该内含子的完整剪接途径。此外，我们还解决了GLMS核酶与其天然配体氨基葡萄糖-6-磷酸结合的结构。我们现在正在研究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做出协同反应。GEMM核糖开关是第一个参与细胞信号传递的RNA的例子，因为它结合了第二个信使信号分子-环双(3‘-5’)二鸟苷酸(c-diGMP)。这个项目的重点是I族自剪接内含子以及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.