Mechanisms and Regulation of Yeast Internal Ribosome Entry Sites

酵母内部核糖体进入位点的机制和调控

• 批准号: 7678947
• 负责人: Wendy Victoria Gilbert
• 金额: $ 24.9万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-13 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7678947
• 关键词: Architecture; Binding Proteins; Biochemical; Biochemical Genetics; Biochemistry; Bioinformatics; Biological; Biological Assay; Cell Survival; Cell physiology; Cells; Collaborations; Complex; Data; Defect; Dissection; Education; Elements; Environment; Future; Gene Expression; Genes; Glucose; Growth; In Vitro; Indium; Internal Ribosome Entry Site; Lead; Link; Location; Mediating; Messenger RNA; Microarray Analysis; Molecular; Molecular Genetics; Osmotic Shocks; Oxidative Stress; Pathway interactions; Peptide Initiation Factors; Physiological; Poly A; Post-Transcriptional Regulation; Proteins; RNA Sequences; RNA-Binding Proteins; RNA-Protein Interaction; Recombinants; Recruitment Activity; Regulation; Research; Research Personnel; Ribosomes; Role; Saccharomyces cerevisiae; Signal Pathway; Starvation; Stress; Students; Sucrose; Training; Translating; Translation Initiation; Translational Regulation; Translations; Viral; Withdrawal; Work; Yeasts; base; comparative; fascinate; human disease; in vivo; insight; interest; mutant; research study; response; skills

My chief scientific interest is post-transcriptional regulation otgene expression. In particular, I am fascinated by the diversity and complexity of RNA-dependent mechanisms of translational control. In the future, I hope to make my own lab an outstanding center for research into the fundamental mechanisms of gene expression, and the defects in gene expression that lead to human diseases. Pursuing my training in Jennifer Doudna's lab at UC Berkeley will provide an outstanding technical education in biochemical dissection of RNA-protein interactions relevant to translation, as well as a diverse and stimulating intellectual environment. I will also develop the professional skills I will need to thrive as an independent investigator in the future, through numerous opportunities to supervise students with diverse scientific strengths and interests. Translation initiation is a crucial point of regulation of eukaryotic gene expression. In response to a variety of environmental insults, cells down-regulate the primary (cap-dependent) mechanism of translation while favoring expression of a select group of genes via alternative initiation mechanisms including direct recruitment of the translation machinery to internal ribosome entry sites (IRESs). Little is known about the molecular basis for cellular IRES activity or for message-specific regulation of these mechanisms. I have identified 24 yeast cellular IRES elements with strong activity both in vitro and in vivo, creating a unique opportunity to combine molecular genetics and biochemistry to determine the molecular basis for, and physiological significance of IRES-dependent gene expression.My aim is to define the molecular functions of cellular IRES RNA sequences and their associated RNA-binding proteins and ultimately, to identify the mechanisms linking stress-related signaling pathways to global and message-specific translational regulation using a combination of biochemical, molecular genetic, and bioinformatic approaches. Results from this work will provide detailed molecular insight into the mechanisms and regulation of internal initiation of translation by diverse cellular IRESs, which is expected to have wide-ranging implications for translational control of eukaryotic gene expression.

我的主要科学兴趣是转录后调节奥特甘烯表达。特别是我着迷 通过转化控制的RNA依赖机制的多样性和复杂性。我希望将来 使我自己的实验室成为研究基因基本机制的杰出中心 表达，以及导致人类疾病的基因表达缺陷。接受我的培训 加州大学伯克利分校的詹妮弗·杜德纳（Jennifer Doudna）的实验室将在生化方面提供出色的技术教育 与翻译相关的RNA蛋白相互作用的解剖以及多样化的智力 环境。我还将发展成为独立研究者所需的专业技能 未来，通过许多机会来监督具有多种科学优势的学生， 利益。 翻译起始是真核基因表达调节的关键点。响应各种 环境侮辱，细胞下调了翻译的主要（帽依赖性）机制，而 通过包括直接的替代起始机制来偏爱精选基因的表达 将翻译机械招募到内部核糖体入口站点（IRESS）。关于 细胞IRE活性的分子基础或这些机制的特定信息调节。我有 鉴定出在体外和体内具有强活性的24个酵母细胞IRES元素，创造了独特的 结合分子遗传学和生物化学的机会，以确定和 IRES依赖性基因表达的生理意义。我的目的是定义分子功能 细胞IRES RNA序列及其相关的RNA结合蛋白，并最终确定 将与压力相关的信号通路连接到全球和消息特定的翻译调节的机制 结合生化，分子遗传和生化方法的结合。这项工作的结果 将提供详细的分子洞察力，了解翻译内部启动的机理和调节 通过各种细胞IRES，预计将对翻译控制具有广泛的影响 真核基因表达。