The Role of Alternative Polyadenylation in Mediating Stress‐ Induced Protein Expression of Hsp70.3

Heat shock protein 70.3 (Hsp70.3) expression is increased in response to cellular stress and plays a cytoprotective role. It has been shown that increased expression of Hsp70.3 expression in the heart is protective against ischemia/reperfusion injury. Recent work from our lab shows that Hsp70.3 expresssion is controlled through coordinated post‐transcriptional regulation by miRNAs and alternative polyadenylation (APA). Results show an APA‐mediated shortening of the Hsp70.3 3’‐UTR upon a stress‐induced increase in expression that facilitates increased protein expression during stress‐induced upregulation of the gene product. This work investigated the mechanisms through which APA‐mediated shortening of the 3’‐UTR contributes to increased protein expression. Our results describe the role of APA on mRNA stability and longevity, micro‐RNA regulation of Hsp70.3, and the role of APA on polysome loading and translational efficiency of the Hsp70.3 transcript. Our results provide a mechanistic understanding of the role APA plays in regulation of Hsp70.3 gene expression and have broad implications for the understanding of APA as a global modulator of gene expression. This work was supported by NIH RO1 HL0901478 (WKJ) and NIH T32 HL007382 (MT).