Regulation and Functions of 3'UTRs in Cellular Stress

3UTR 在细胞应激中的调节和功能

• 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
• 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' 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

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.

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