Stress-Responsive RNA Regulons in Cryptococcus neoformans

新型隐球菌中的应激反应性 RNA 调节子

基本信息

批准号：
8293351
负责人：
John C Panepinto
金额：
$ 34.38万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8293351
关键词：
3&apos Untranslated Regions Address Algorithms Antifungal Agents Binding Binding Proteins Biological Assay Cell Nucleus Cell Wall Communities Complement Complex Copper Cryptococcus neoformans Cryptococcus neoformans infection Data Elements Exhibits Family Future Gene Expression Gene Expression Regulation Generations Genes Genetic Goals HIV Infections Homologous Gene Indium Iron Maintenance Maps Mediating Mediator of activation protein Meningitis Messenger RNA Microarray Analysis Molecular Nutrient Operon Organism Oxidative Stress Pathogenesis Pathogenicity Pathway interactions Phenotype Plague Post-Transcriptional Regulation Protein Binding Proteins RNA RNA Recognition Motif RNA-Binding Proteins RNA-Protein Interaction Regulon Ribosomal Proteins Role Saccharomyces cerevisiae Specificity Stress Structure Temperature Testing Therapeutic Transcript Untranslated Regions Virulence Work base fungus inhibitor/antagonist mRNA Transcript Degradation mouse model mutant nitrosative stress novel pathogen research study response ribosomal protein 3 small molecule stress tolerance stressor

项目摘要

DESCRIPTION (provided by applicant): The pathogenic fungus Cryptococcus neoformans has emerged as the primary cause of community acquired meningitis in regions of the world plagued by HIV infection. Our previous studies have demonstrated a role for post-transcriptional gene regulation in stress tolerance. Our long term goal is to systematically map the protein-RNA interactions that C. neoformans requires for the maintenance of stress tolerance and pathogenicity. We hypothesize that these RNA-protein interactions contribute to the adaptability of C. neoformans, conferring agility to gene expression independent of the nucleus. In this proposal, our focus is two-pronged: First we will identify the RNA binding protein that is interacting with a GGAUG cis element in ribosomal protein transcripts found up-regulated in the ccr4? mutant, and determine its role in stress tolerance and pathogenicity. Second, we will determine the role of the C. neoformans PUF family of RNA binding proteins in stress tolerance and pathogenicity. For both the GGAUG-binding protein and the PUF proteins, we will determine the complement of transcripts that interact with each, allowing us to assemble their respective RNA regulons. Future studies will then build on this work and expand to additional classes or RNA binding proteins. Ultimately, the identification of RNA-protein interactions important for C. neoformans stress tolerance and pathogenicity will provide us with specific targets for novel small-molecule based therapeutics.

描述（由申请人提供）：致病性真菌新型隐球菌已成为世界上受艾滋病毒感染困扰的地区社区获得性脑膜炎的主要原因。我们之前的研究已经证明了转录后基因调控在应激耐受中的作用。我们的长期目标是系统地绘制新型隐球菌维持应激耐受性和致病性所需的蛋白质-RNA 相互作用图谱。我们假设这些RNA-蛋白质相互作用有助于新型隐球菌的适应性，赋予其独立于细胞核的基因表达的灵活性。在这个提案中，我们的重点有两个方面：首先，我们将鉴定与核糖体蛋白转录物中的 GGAUG 顺式元件相互作用的 RNA 结合蛋白，该蛋白在 ccr4? 中被发现上调？突变体，并确定其在胁迫耐受性和致病性中的作用。其次，我们将确定 RNA 结合蛋白的新型隐球菌 PUF 家族在胁迫耐受性和致病性中的作用。对于 GGAUG 结合蛋白和 PUF 蛋白，我们将确定与每种蛋白相互作用的转录物的互补体，从而使我们能够组装它们各自的 RNA 调节子。未来的研究将以这项工作为基础，并扩展到其他类别或 RNA 结合蛋白。最终，对新型隐球菌应激耐受性和致病性重要的RNA-蛋白质相互作用的鉴定将为我们提供新型小分子治疗的具体靶点。