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

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FONTE

The Federation of American Societies for Experimental Biology

RESUMO

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 β-galactosidase (βGal) 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/βGal mRNA increased significantly by 3.7-fold in contracting vs. quiescent cardiocytes, but ODC/βGal mRNA was unchanged. Contraction increased c-jun/βGal 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 βGal 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.—Spruill, L. S., McDermott, P. J. Role of the 5′-untranslated region in regulating translational efficiency of specific mRNAs in adult cardiocytes.

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