University of Massachusetts Medical School Faculty Publications
Title
FUS/TLS assembles into stress granules and is a prosurvival factor during hyperosmolar stress
UMMS Affiliation
Department of Neurology
Publication Date
2013-04-27
Document Type
Article
Subjects
RNA-Binding Protein FUS; Stress, Physiological
Disciplines
Biochemistry, Biophysics, and Structural Biology | Cellular and Molecular Physiology | Neurology
Abstract
FUsed in Sarcoma/Translocated in LipoSarcoma (FUS/TLS or FUS) has been linked to several biological processes involving DNA and RNA processing, and has been associated with multiple diseases, including myxoid liposarcoma and amyotrophic lateral sclerosis (ALS). ALS-associated mutations cause FUS to associate with stalled translational complexes called stress granules under conditions of stress. However, little is known regarding the normal role of endogenous (non-disease linked) FUS in cellular stress response. Here, we demonstrate that endogenous FUS exerts a robust response to hyperosmolar stress induced by sorbitol. Hyperosmolar stress causes an immediate re-distribution of nuclear FUS to the cytoplasm, where it incorporates into stress granules. The redistribution of FUS to the cytoplasm is modulated by methyltransferase activity, whereas the inhibition of methyltransferase activity does not affect the incorporation of FUS into stress granules. The response to hyperosmolar stress is specific, since endogenous FUS does not redistribute to the cytoplasm in response to sodium arsenite, hydrogen peroxide, thapsigargin, or heat shock, all of which induce stress granule assembly. Intriguingly, cells with reduced expression of FUS exhibit a loss of cell viability in response to sorbitol, indicating a prosurvival role for endogenous FUS in the cellular response to hyperosmolar stress. J. Cell. Physiol. (c) 2013 Wiley Periodicals, Inc.
DOI of Published Version
10.1002/jcp.24395
Source
J Cell Physiol. 2013 Apr 27. doi: 10.1002/jcp.24395. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
Journal of cellular physiology
PubMed ID
23625794
Repository Citation
Sama, Reddy Ranjith R.; Ward, Catherine; Kaushansky, Laura J.; Lemay, Nathan; Ishigaki, Shinsuke; Urano, Fumihiko; and Bosco, Daryl A., "FUS/TLS assembles into stress granules and is a prosurvival factor during hyperosmolar stress" (2013). University of Massachusetts Medical School Faculty Publications. 69.
https://escholarship.umassmed.edu/faculty_pubs/69