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.

Public Health Relevance

Stress response mechanisms help cells survive under stress and restore homeostasis during recovery from stress. We plan to examine a newly discovered stress response mechanism in which 3?UTRs are regulated by stress. The result of this project will help understand the etiology of human ailments associated with cellular stress.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM129069-03
Application #
10218476
Study Section
Molecular Genetics A Study Section (MGA)
Program Officer
Reddy, Michael K
Project Start
2018-09-01
Project End
2022-08-31
Budget Start
2020-05-01
Budget End
2020-08-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
075524595
City
Philadelphia
State
PA
Country
United States
Zip Code
19104