Structure and Function Studies on RNA Splicing Endonuclease

RNA是一种将遗传信息从DNA传递到细胞其他部分的分子。RNA是DNA的副本，但与DNA双螺旋不同，每个基因的RNA副本形成独特的三维形状，强烈影响其行为，包括它如何与蛋白质相互作用。本项目利用x射线晶体学等生化工具来了解凸起-螺旋-凸起RNA蛋白复合物的三维结构。凸起-螺旋-凸起RNA结构基序特异性地与一种称为剪接内切酶的蛋白质酶结合，导致RNA两个特定位置的化学键断裂。这个细胞过程是使RNA分子成熟的必要步骤，就像电影剪辑的方式一样。这些基序通常存在于含有古生菌tRNA转录本的内含子的外显子-内含子连接处以及古生菌前体核糖体RNA转录本的加工茎中。本研究将描述RNA与蛋白质结合以及蛋白质催化的RNA裂解反应的化学原理。从这项研究中获得的知识将加强生物化学和分子生物学的课堂教学。该项目还将为高中生、本科生、研究生和博士后提供研究机会。

RNA is the molecule that carries genetic information from DNA to the rest of the cell. RNA is a copy of DNA, but unlike the DNA double helix, the RNA copy of each gene forms a unique three-dimensional shape that strongly influences its behavior, including how it interacts with proteins. This project uses x-ray crystallography and other biochemical tools to learn the three-dimensional structure of the bulge-helix-bulge RNA protein complexes. The bulge-helix-bulge RNA structural motif specifically binds to a protein enzyme called the splicing endonuclease, leading to breakage of chemical bonds at two specific locations of the RNA. This cellular process is an obligatory step required to maturate RNA molecules, much like the way movie films are edited. The motifs are commonly found at the exon-intron junctions in intron containing archaeal tRNA transcripts and in the processing stems of archaeal precursor ribosomal RNA transcripts. This research will delineate the chemical principles involved in association of RNA and proteins and protein catalyzed RNA cleavage reactions. Knowledge obtained from this research will enhance classroom teaching of both biochemistry and molecular biology. This project will also provide research opportunities for high school, undergraduate, graduate and post doctoral students.