HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data Buy All Versions of this Article: fj.08-128447v1 23/9/2879    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Spruill, L. S. Articles by McDermott, P. J. PubMed PubMed Citation Articles by Spruill, L. S. Articles by McDermott, P. J.

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

Laura S. Spruill^* and Paul J. McDermott^*,,1

^* Gazes Cardiac Research Institute, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA; and the

Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina, USA

¹ Correspondence: Gazes Cardiac Research Institute, Rm. 303, Strom Thurmond Biomedical Research Bldg., 114 Doughty St., Charleston, SC 29403, USA. E-mail: mcdermp{at}musc.edu

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.

Key Words: cardiac hypertrophy • protein biosynthesis • polyribosomes • peptide chain initiation