The Stress-induced Heat Shock Protein 70.3 Expression is Regulated by a Dual-component Mechanism Involving Alternative Polyadenylation and HuR.
Biochimica Et Biophysica Acta
Heat shock protein 70.3 (Hsp70.3) expression increases in response to cellular stress and plays a cytoprotective role. We have previously shown that Hsp70.3 expression is controlled through coordinated post-transcriptional regulation by miRNAs and alternative polyadenylation (APA), and APA-mediated shortening of the Hsp70.3 3'-UTR facilitates increased protein expression. A stress-induced increase in Hsp70.3 mRNA and protein expression is accompanied by alternative polyadenylation (APA)-mediated truncation of the 3'UTR of the Hsp70.3 mRNA transcript. However, the role that APA plays in stress-induced expression of Hsp70.3 remains unclear. Our results show that APA-mediated truncation of the Hsp70.3 3'UTR increases protein expression through enhanced polyribosome loading. Additionally, we demonstrate that the RNA binding protein HuR, which has been previously shown to play a role in mediating APA, is necessary for heat shock mediated increase in Hsp70.3 mRNA and protein. However, it is somewhat surprising to note that HuR does not play a role in APA of the Hsp70.3 mRNA, and these two regulatory events appear to be mutually exclusive regulators of Hsp70.3 expression. These results not only provide important insight to the regulation of stress response genes following heat shock, but also contribute an enhanced understanding of how alternative polyadenylation contributes to gene regulation. (Copyright © 2015. Published by Elsevier B.V.)
Kraynik S, Gabanic A, Anthony S, Kelley M, Paulding W, Tranter M, et al. The stress-induced heat shock protein 70.3 expression is regulated by a dual-component mechanism involving alternative polyadenylation and HuR. Biochimica Et Biophysica Acta [serial on the Internet]. (2015, Feb 26), [cited March 17, 2015]; Available from: MEDLINE.
Paulding, Waltke R.; Kraynik, S. M.; Gabanic, A.; Anthony, S. R.; Kelley, M.; Roessler, A.; McGinness, M.; and Tranter, M., "The Stress-induced Heat Shock Protein 70.3 Expression is Regulated by a Dual-component Mechanism Involving Alternative Polyadenylation and HuR." (2015). Faculty Scholarship. Paper 1.