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.
|Effective start/end date||9/1/18 → 8/31/20|
- National Institute of General Medical Sciences: $318,000.00
- National Institute of General Medical Sciences: $170,580.00
- National Institute of General Medical Sciences: $261,665.00
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.