mRNA decay mechanisms for ER stress recovery

内质网应激恢复的 mRNA 衰减机制

• 批准号: 7673496
• 负责人: JULIE HOLLIEN
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7673496
• 关键词: Address; Affect; Alzheimer' s Disease; Area; Cell Cycle Regulation; Cells; Circadian Rhythms; Collection; Development; Diabetes Mellitus; Disease; Endoplasmic Reticulum; Environment; Equilibrium; Event; Failure; Future; Genomics; Goals; Homeostasis; Human; Immune response; Infection; Laboratories; Learning; Life; Link; Long-Term Effects; Mediating; Membrane; Messenger RNA; Monitor; Mutation; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Output; Pathway interactions; Peptide Signal Sequences; Physiological; Play; Postdoctoral Fellow; Process; Proteins; Recovery; Regulation; Research; Research Personnel; Resources; Role; Secretory Cell; Specificity; Stress; Substrate Specificity; Techniques; Testing; Transcriptional Regulation; Translating; Translations; Virus Diseases; Work; acute stress; coping; design; endonuclease; human disease; insight; interest; mRNA Decay; mRNA Stability; polypeptide; programs; protein expression; research study; response

This project is designed to build upon work I have done as a postdoctoral scholar, to follow exciting leads opened up by the discovery of a new mechanism cells employ to recover from stress, and expand these studies into new areas that I will study as an independent investigator. My goals are draw upon the substantial resources and expertise at UCSF that will allow me to learn new techniques and expand my research, and in the longer term to develop my own research program focused on mRNA regulation and its relationship to localization and recovery from stress. As a postdoc in Jonathan Weissman's laboratory at UCSF, I have initially characterized a new pathway by which cells degrade mRNAs localized to the endoplasmic reticulum as a way of coping with folding stress in this compartment. There are many physiological and mechanistic aspects of this pathway that are unexplored and are likely to provide insight into how cells survive acute stress, how a specific endonuclease participates in the decay of a broad spectrum of mRNAs, and how localization affects mRNA stability and regulation. The research described in this application is designed to address each of these issues directly, using a combination of genomic and smaller scale experiments. The research outlined here will further our understanding of how cells survive and adapt to stress in the ER, a condition that has been linked to a variety of human diseases, including diabetes and Alzheimer's disease, as well as viral infection. Understanding how cells cope with this situation will have direct relevance to our understanding of the mechanisms of these diseases. For example, the relationship between obesity and type 2 diabetes has been proposed to be mediated by ER stress and in particular Ire1, a protein whose function will be directly investigated in this study.

这个项目是建立在我作为博士后学者所做的工作的基础上，遵循令人兴奋的线索