关于新型核开关SAM-VI的结构与作用机制研究

核开关是mRNA 5’-端非编码区的一段保守序列，通过与配体的相互作用改变自身的构象，从而在转录或翻译阶段调控后续基因的表达。SAM是生物体内非常重要的甲基转移中介分子。SAM核开关是目前种类最多的核开关，也是最重要的核开关之一，负责调控SAM合成酶的表达，控制SAM的合成。最近耶鲁大学Breaker教授课题组通过全基因组分析发现一类新型核开关—————SAM-VI核开关。该核开关与已知的SAM-III核开关具有相似的二级结构，但在识别配体的中心大内环区，核苷酸序列和数目又各不相同。本项目将采用X-射线晶体学的方法，结合分子生物学、化学生物学等方法，研究该核开关与配体的相互作用方式、对后续基因的调控机制，探讨该核开关与SAM-III核开关的异同，进而寻找不同SAM核开关在进化和起源上的相互关系，为进一步开发SAM核开关的应用提供更多的理论基础，也为RNA世界提供更多的信息。

Riboswitches are the conserved RNA elements in the 5’-end untranslated region of mRNA, which can specifically interact with the ligand and change it’s own conformation to control gene expression in translation or transcription level. SAM is an important molecule working as the universal methyl currency in all the living organisms. SAM riboswitches can interact with SAM to regulate the expression of SAM synthetase and control the synthesis of SAM. SAM riboswitches are one of the most important riboswitch families, which contain the highest number of riboswitch classes. Recently, Prof. Breaker from Yale University reported a new riboswitch, SAM-VI riboswitch through comparative sequence analysis method. SAM-VI riboswitch has similar second structural elements with SAM-III riboswitch, but the number and the sequences of nucleotides in the key internal loop that interact with the ligand SAM are different. In this project, we will use X-crystallography method, combining with molecular biology method, chemical biology method and other methods to solve the structure of SAM-VI riboswitch to explore the ligand recognition pattern and the regulation mechanism of SAM-VI riboswitch, to compare it with SAM-III riboswitch to seek the relationship in the origin and the evolution between different SAM riboswitch classes. These researches will provide more theory basis for the application of SAM riboswitches and more information for RNA world.