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The Role of DEAD-box Proteins in Gene Expression

DEAD-box 蛋白在基因表达中的作用

基本信息

批准号：
9902525
负责人：
Elizabeth J Tran
金额：
$ 31.21万
依托单位：
PURDUE UNIVERSITY
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：
2011-04-01 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9902525
关键词：
ATP Hydrolysis Area Binding Binding Sites Biochemical Biogenesis Bioinformatics Biological Biological Assay Biological Process Biology Carbon Cells Chromatin Coupled Couples Coupling DNA Enzymes Exhibits Failure Funding Galactose Galanin Gene Expression Gene Expression Regulation Genes Genetic Screening Genetic Transcription Genomic Instability Glucose Goals Hand Human Hybrids Intervention Knowledge Life Light Link Malignant Neoplasms Maps Mediating Messenger RNA Metabolic Metabolic Control Metabolic Diseases Metabolism Microscopy Molecular Nuclear Nuclear Export Nuclear Import Nutrient Nutritional status Nutritive Value Oncogenes Orthologous Gene Pathway interactions Peptide Signal Sequences Phosphorylation Poly(A)+ RNA Proteins Quality Control RNA RNA Decay RNA Helicase RNA Polymerase II RNA Splicing RNA Stability RNA helicase A Reporter Repression Research Resistance Role Saccharomyces cerevisiae Series Source Structure Techniques Testing Time Transcript Transcription Repressor Transcriptional Regulation Translations Untranslated RNA base chemotherapy helicase human disease in vivo innovation insight interdisciplinary approach mutant novel prevent protein complex response transcription factor

项目摘要

ABSTRACT RNA helicases are a class of enzymes that modulate RNA structure in living cells, functioning in every aspect of RNA biology from transcription to decay. However, the precise biological function of the vast majority of the ~40 eukaryotic RNA helicases is largely unknown. In the previous funding cycle, we utilized a powerful multidisciplinary approach to provide biological and biochemical characterization of the RNA helicase Dbp2 in S. cerevisiae. We specifically focused on this enzyme because the human ortholog of Dbp2, DDX5, is functionally enigmatic oncogene. These studies revealed a novel role for an RNA helicase in cellular metabolism and elucidated timely insights into lncRNA and R-loop biology. However, key questions remain regarding the precise function of Dbp2/hDDX5 and, by extension, the functions of all of the ~40 DEAD-box helicases. These questions are: 1. What are the RNA structures that Dbp2 targets? 2. How does Dbp2 sense the nutritional status of the cell? 3. How does a single RNA helicase regulate a specific gene expression network? Our central hypothesis is that Dbp2 modulates the secondary structure of specific RNA Pol II transcripts to promote termination and repression of R-loop formation in response to nutritional availability. The objective of this application is to determine how Dbp2 couples nutritional status to metabolic gene regulation as a direct extension of our prior insights. We propose to test this hypothesis with three, focused Specific Aims, which integrate newly established and innovative strategies with proven experimental techniques. In Aim 1, we will define the precise RNA substrates for enzymatic rearrangement by Dbp2. In Aim 2, we will determine how subcellular localization of Dbp2 is regulated in response to nutritional status. In Aim 3, we will determine the mechanism for metabolic gene regulation by Dbp2 and lncRNAs. This research is relevant to multiple aspects of RNA biology, gene regulation, and cancer.

摘要