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Functional genomics of the dynamic molecular network controlling mRNA translation and decay

控制 mRNA 翻译和衰变的动态分子网络的功能基因组学

基本信息

批准号：
10357812
负责人：
NICHOLAS T INGOLIA
金额：
$ 30.4万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10357812
关键词：
Address Affect Binding Binding Proteins Catalogs Cell physiology Cells Complement Cues Cytosol Disease Environment Gene Expression Genes Genetic Genetic Transcription Genetic Translation Goals Growth Homeostasis Human Individual Learning Link Mammalian Cell Maps Measures Mediating Messenger RNA Modeling Molecular Pathologic Phosphorylation Physiological Physiological Adaptation Physiology Play Post-Transcriptional Regulation Proteins RNA RNA Binding RNA-Binding Proteins RNA-Protein Interaction Regulation Regulon Role Saccharomycetales Signal Pathway Signal Transduction Stimulus Stress Surveys Switch Genes Techniques Transcript Translations Work base biological systems disease phenotype environmental change environmental stressor functional genomics genetic regulatory protein in vivo insight mRNA Decay new therapeutic target programs protein profiling response transcription factor

项目摘要

ABSTRACT Cells respond to environmental changes and stresses by modulating the translation and decay of mRNAs in the cytosol. This post-transcriptional regulation is critical for maintaining proper cellular physiology. Often, these regulatory programs protect cells from pathological stresses. In other cases, however, maladaptive responses underlie disease phenotypes. Understanding these dynamic, environmentally responsive post-transcriptional regulatory programs is critical for understanding cell physiology and promises novel therapeutic targets to support protective responses and suppress damaging ones. Recent work has catalogued hundreds of mRNA-binding proteins. Our understanding of how these proteins affect the mRNAs they bind has lagged behind studies that enumerate these proteins, and we generally lack an understanding of their broader role in the cell. Our motivating hypothesis is that many of these proteins target speciﬁc transcripts and regulate their translation and stability in a coordinated fashion in response to environmental and intracellular cues. Indeed, we know of regulatory proteins that bind transcripts encoding functionally related genes and switch between promoting decay or promoting translation in response to regulatory phosphorylation. We believe that this represents a more widespread model. The broad scientiﬁc goal of this proposal is to elucidate the functional networks of post- transcriptional regulation in the cell. We will apply high-throughput and unbiased approaches to work outward from mRNA-binding proteins in order to identify the signals that control their activity, the upstream and downstream factors that mediate their effect, and the regulatory programs that they control. Our work will reveal the general principles governing how and why gene expression is controlled post-transcriptionally. We will also develop approaches that can be transferred to address this question in a wide array of other biological systems.

摘要