Regulation and Functions of 3'UTRs in Cellular Stress

3UTR 在细胞应激中的调节和功能

基本信息

批准号：
10249371
负责人：
BIN TIAN
金额：
$ 36.5万
依托单位：
WISTAR INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10249371
关键词：
3&apos Untranslated Regions Address Arsenic Bioinformatics Biological Assay Cardiovascular Diseases Cells Cellular Stress Code Complex Cytoplasm Diabetes Mellitus Disease Elements Environmental Exposure Etiology Eukaryota Exposure to Genes Genetic Transcription Genomics Goals Heat-Shock Response Homeostasis Human Hypoxia Individual Lead Malignant Neoplasms Mediating Messenger RNA Metabolism MicroRNAs Modeling Molecular Muscle Fibers Myoblasts Neurons Nuclear Export Nutritional Oxidative Stress Play Polyadenylation Positioning Attribute Post-Transcriptional Regulation Post-Translational Protein Processing Pre-mRNA Polyadenylation Factor Protein Biosynthesis Protein Isoforms Proteins RNA RNA Polymerase II RNA analysis Recovery Regulation Reporter Research Role Shock Site Stress System Toxin Transcript Translations Undifferentiated base biological adaptation to stress cancer cell cell type endoplasmic reticulum stress environmental change genome-wide human disease mRNA Stability nervous system disorder novel preservation protein expression recruit response stress granule stressor

项目摘要

SUMMARY Environmental changes and exposure to toxins lead to cellular stress of different kinds, such as oxidative stress, heat shock, cold shock, hypoxia, nutritional stress, endoplasmic reticulum stress, etc. Cellular stress has been implicated in many human diseases, such as cardiovascular diseases, neurological disorders, diabetes, and various forms of cancer. A number of stress response mechanisms at both transcriptional and post-transcriptional levels help cells survive under stress and restore homeostasis during recovery from stress. We recently found that arsenic stress (AS), a commonly used stress model, elicits global shortening of 3’UTR through alternative polyadenylation, a widespread post-transcriptional mechanism in eukaryotes. Our long-term goal is to understand the mechanisms and consequences of 3’UTR regulation in cellular stress. In this proposal, we plan to 1) elucidate the mechanism(s) behind 3’UTR shortening in AS, 2) examine the consequences of AS-induced 3’UTR shortening for mRNA metabolism, and 3) analyze stress- induced 3’UTR changes in different cell contexts and by different stressors. The result of this project will elucidate a novel adaptive stress response mechanism, and help understand the etiology of human ailments associated with cellular stress.

概括环境变化和暴露于毒素会导致不同种类的细胞应激，例如氧化压力，热休克，冷休克，缺氧，营养应激，内质网应激等。细胞应激在许多人类疾病中隐含着，例如心血管疾病，神经系统疾病，糖尿病和各种形式的癌症。转录和转录后水平有助于细胞在压力下生存并恢复从压力。我们最近发现，砷应力（AS）是一种常用的应力模型，引起了全球缩短通过替代聚烯基化的3'UTR，这是真核生物中的宽度后转录机制。我们的长期目标是了解3'UTR调节在细胞中的机制和后果压力。在此提案中，我们计划1）阐明3'UTR缩短AS的机制，2）检查AS诱导的3'UTR缩短对mRNA代谢的后果，3）分析应激 - 在不同的细胞环境和不同的压力源中引起的3'UTR变化。这个项目的结果将阐明一种新型的适应性应激反应机制，并有助于理解人类的病因与细胞应激相关的疾病。