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Post‐transcriptional regulation of Hsp70.3 expression by miRNAs and alternative polyadenylation
Author(s) -
Tranter Michael,
McGuinness Michael,
Ren Xiaoping,
Helsley Robert N.,
Paulding Waltke R.,
Haar Lauren,
Brokamp Cole,
Jones W. Keith
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1090.14
Subject(s) - polyadenylation , microrna , hsp70 , three prime untranslated region , biology , gene expression , untranslated region , regulation of gene expression , messenger rna , microbiology and biotechnology , gene , heat shock protein , genetics
Expression of heat shock protein 70.3 (Hsp70.3) in the myocardium is protective against ischemia/reperfusion (I/R) injury, but is regulated by 3′‐UTR‐mediated post‐transcriptional suppression. This work investigated the hypothesis that coordinated actions by miRNAs and alternative polyadenylation (APA) exert post‐transcriptional regulation on Hsp70.3 expression in the myocardium . Results The 3′‐UTR of the Hsp70.3 mRNA sequence was predicted to harbor multiple miRNA binding sites and APA signals. In addition to identifying two stress‐regulated miRNAs that modulate Hsp70.3 expression, we show the expression of four distinct populations of APA Hsp70.3 transcripts in the heart. Results show a significant and preferential increase in Hsp70.3 mRNA transcripts with shortened 3′‐UTRs following ischemic stimuli. This APA‐mediated shortening of the Hsp70.3 3′‐UTR results in the removal of a regulatory miRNA binding site and increased gene expression. Discussion Our results indicate a potentially important role for APA in regulation of cardioprotective gene programs in the heart. In addition, it appears these processes may be coordinated with miRNA‐mediated regulation. Investigations are currently ongoing to determine the mechanisms mediating APA site selection and the role of miRNAs in this process. This work was supported by NIH RO1 HL0901478 (WKJ) and NIH T32 HL007382 (MT).