Structures of RNA processing and Silencing Enzymes in Prokaryotes

原核生物中 RNA 加工和沉默酶的结构

基本信息

批准号：
8622205
负责人：
Hong Li
金额：
$ 26.86万
依托单位：
FLORIDA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-01 至 2016-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8622205
关键词：
Adenylate Cyclase Antibiotic Resistance Antimicrobial Resistance Archaea Archaeal Genome Bacteria Bacteriophages Beryllium Binding Biochemical Biogenesis Catalytic Domain Cleaved cell Clostridium tetani Clustered Regularly Interspaced Short Palindromic Repeats Complex DNA Data Diagnostic Docking Elements Environment Enzymes Epidemic Epidemiologic Studies Equilibrium Family Future Genes Genetic Materials Haemophilus influenzae Helicobacter pylori Human Immunity Individual Infection Invaded Laboratories Learning Maintenance Mediating Memory Meningitis Microbe Molecular Molecular Biology Mycobacterium tuberculosis Nature Neisseria Nucleic Acids Obstruction Pathogen detection Pathway interactions Pattern Plasmids Polymerase Predatory Behavior Process Production Prokaryotic Cells Property Proteins RNA RNA Interference RNA Processing Resolution Ribonucleoproteins Role Salmonella typhi Site Small RNA Specificity Staphylococcus aureus Structure System Vibrio vulnificus Viral Work Yersinia pestis adaptive immunity base combat design endonuclease genetic element human BCAR1 protein insight microbial novel particle pathogen reconstitution research study three dimensional structure three-dimensional modeling virus host interaction

项目摘要

DESCRIPTION (provided by applicant): Like eukarya, bacteria and archaea have evolved a variety of defense systems to protect themselves from selfish genetic elements (phages, transposons, and plasmids). On the other hand, successfully disseminated mobile elements can benefit the bacterial hosts, for instance, by introducing antibiotics resistant genes. Understanding the defense systems, therefore, not only offers insights on prokaryotic molecular biology principles but may also provide new strategies to defend the antibiotics resistance epidemics. Recently, a novel widespread defense system that functions on a completely different principle than those previously known was discovered. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) are found in 40% of bacterial and 90% of archaeal genomes that confers a small RNA-based prokaryotic immunity system. In this remarkable process, DNA short sequences capturing the memories of past infection are transcribed and processed into small RNA molecules that then pattern with proteins to silence the new invader nucleic acids. This proposal will investigate the molecular mechanisms of two currently identified CRISPR machineries, that for production of the CRISPR RNAs and that for silencing invading RNA. Experimental aims are designed to provide a comprehensive understanding of the structural and functional properties of the processing endonuclease and the RNA silencing complex. Relevance: The CRISPR elements of bacteria and archaea provide an important vehicle for maintaining a balance in microbial environments through exchange and destruction of genetic materials. CRISPR elements are found in medically important bacteria that include but not limited to Yersinia pestis, Mycobacterium tuberculosis, Haemophilus influenzae, Helicobacter pylori, Neisseria meningitides, Vibrio vulnificus, Staphylococcus aureus, Salmonella Typhi and Clostridium tetani. A thorough understanding of the CRISPR immunity has important implications in studies of bacterial pathogen spread, antimicrobial resistance, and host-virus interactions. The proposed molecular mechanisms of this novel pathway may be exploited for building specific immunity against undesirable genetic elements such as those spreading antibiotics resistance genes.

描述（由申请人提供）：与真核生物一样，细菌和古细菌也进化出了多种防御系统，以保护自己免受自私遗传因素（噬菌体、转座子和质粒）的侵害。另一方面，成功传播的移动元件可以使细菌宿主受益，例如通过引入抗生素抗性基因。因此，了解防御系统不仅可以提供对原核分子生物学原理的见解，还可以提供防御抗生素耐药性流行病的新策略。最近，人们发现了一种广泛传播的新型防御系统，其工作原理与之前已知的系统完全不同。成簇规则间隔短回文重复序列 (CRISPR) 存在于 40% 的细菌和 90% 的古细菌基因组中，赋予基于小 RNA 的原核免疫系统。在这个非凡的过程中，捕获过去感染记忆的 DNA 短序列被转录并加工成小 RNA 分子，然后与蛋白质一起形成图案，以沉默新的入侵者核酸。该提案将研究目前已发现的两种 CRISPR 机器的分子机制，即用于生产 CRISPR RNA 的机器和用于沉默入侵 RNA 的机器。实验目的旨在全面了解核酸内切酶和 RNA 沉默复合物的结构和功能特性。相关性：细菌和古细菌的 CRISPR 元件通过交换和破坏遗传物质，为维持微生物环境的平衡提供了重要的工具。 CRISPR元件存在于医学上重要的细菌中，包括但不限于鼠疫耶尔森氏菌、结核分枝杆菌、流感嗜血杆菌、幽门螺杆菌、脑膜炎奈瑟菌、创伤弧菌、金黄色葡萄球菌、伤寒沙门氏菌和破伤风梭菌。深入了解 CRISPR 免疫对于细菌病原体传播、抗菌素耐药性和宿主-病毒相互作用的研究具有重要意义。这种新途径的分子机制可用于建立针对不良遗传元件（例如传播抗生素抗性基因的遗传元件）的特异性免疫力。