Journal of Biotechnology & Biomaterials
Open Access

Abstract

Duchenne Muscular Dystrophy (DMD) is the most common X-linked genetic disorder that occurs 1 in every 3500 male child birth worldwide. There is no strategy available to cure the fatal disease. DMD results from the mutation in the dystrophin gene that leads to formation of non-functional or truncated dystrophin. Dystrophin is the integral component of dystrophin associated protein complex which links between actin filament and extracellular matrix and therefore maintains sarcolemmal integrity in muscle fiber. Up-regulation of utrophin, the autosomal homologue of dystrophin has been suggested as one of the promising strategies for DMD treatment. In adult utrophin expression however is confined to neuromuscular and myotendinous junction. Therefore understanding the regulation of utrophin expression has therapeutic importance. Although the transcriptional regulation of utrophin-A, the skeletal muscle specific isoform has been well studied, limited works have been focused on its post-transcriptional regulation. Previous studies suggested an Internal Ribosome Entry Site (IRES) in utrophin-A 5�-UTR. Repression of translation has also been demonstrated with this 5�-UTR. In order to improve the understanding, the present study compared contribution of cap-dependent as well as cap-independent translation with utrophin-A 5�-UTR with m7G and A-capped RNA transfection based approach. Compared to well studied encephalomyocarditis virus IRES, capindependent translation with utrophin-A 5�-UTR is weak. However, its contribution becomes significant as cap-dependent translation is severely repressed with it. We further identified two cis-acting elements and one upstream open reading frame in utrophin-A 5�-UTR responsible for translation repression. The repressor elements may be targeted for up-regulation of utrophin-A expression.

Biography

Email: trinathghosh@gmail.com