Role of the 5′‐untranslated region in regulating translational efficiency of specific mRNAs in adult cardiocytes

Abstract

It has been hypothesized that translational efficiency is determined by the amount of secondary structure in the 5'-untranslated region (5'-UTR) of mRNA. Here, we examined whether specific 5'-UTRs with excessive secondary structure selectively regulate translational efficiency in adult cardiocytes. Recombinant adenoviruses were generated to express reporter mRNAs consisting of the 5'-UTR derived from c-jun or ornithine decarboxylase (ODC) fused to beta-galactosidase (betaGal) coding sequence. Each adenovirus expressed GFP mRNA as a control for 5'-UTRs with minimal secondary structure. Subsequently, cardiocytes were electrically stimulated to contract at 1 Hz to accelerate protein synthesis as compared to quiescent controls. Translational efficiency was calculated by measuring protein expression as a function of mRNA levels. Translational efficiency of c-jun/betaGal mRNA increased significantly by 3.7-fold in contracting vs. quiescent cardiocytes, but ODC/betaGal mRNA was unchanged. Contraction increased c-jun/betaGal mRNA levels in polyribosomes by 2.3-fold, which indicates that translational efficiency was enhanced by mobilization. A short, unstructured 5'-UTR was sufficient for efficient translation of betaGal mRNA in quiescent and contracting cardiocytes. GFP mRNA produced similar results. These studies demonstrate that the 5'-UTR functions as a determinant of translational efficiency of specific mRNAs, such as c-jun, that regulate growth of the adult cardiocyte.