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

FASEB J. 2009 Sep;23(9):2879-87. doi: 10.1096/fj.08-128447. Epub 2009 May 5.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 5' Untranslated Regions / genetics*
  • Adenoviridae / genetics
  • Animals
  • Cats
  • Cell Proliferation
  • Myocytes, Cardiac / cytology
  • Protein Biosynthesis*
  • Proto-Oncogene Proteins c-jun / genetics
  • RNA, Messenger / analysis*
  • Transduction, Genetic

Substances

  • 5' Untranslated Regions
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger