The role of the 5'-untranslated region in regulating the expression of utrophin in skeletal muscle cells

Abstract

Up-regulating utrophin expression at the sarcolemma is thought to be a key therapeutic approach in the fight against DMD. Utrophin was found to have two isoforms which differ mainly in their 5'-untranslated regions. Effects of the utrophin 5'UTRs on reportergene expression in cell culture and muscle injection experiments were assayed by measuring both reporter transcript and protein levels. Translation efficiencies were estimated by calculating transcript to protein ratios. Our results indicate that there is considerable translation inhibition in control muscle. In comparison, significantly divergent translation efficiencies in regenerating muscle indicate a direct correlation between transcript and protein levels, as seen in cell culture. Furthermore, low levels of translational inhibition are present in adult mdx mice, yet it is significantly de-repressed in young mdx muscle. Taken together, our results suggest that, via the utrophin 5'UTRs, translational regulation is involved in regulating utrophin expression.