Structural diversity despite strong evolutionary conservation in the 5 '-untranslated region of the P-type dystrophin transcript

Analysis of the 5'-flanking regions of the Purkinje (P-) dystrophin genes a nd mRNAs in different species revealed strong sequence conservation but fun ctional diversity. Multiple transcription initiation sites were identified in cerebella and muscles, tissues expressing P-dystrophin. The predominant initiation site was conserved, with another muscle-specific site located up stream. Despite sequence homology, significant tissue- and species-specific structural diversity in the P-type 5'-ends exists, including alternative s plicing within the 5'-untranslated region combined with alternative splicin g of intron 1. One amino terminus is conserved in mammals and, to a lesser extent, in chicken. However, alternative usage of ATG codons may result in a choice of N-termini or translation of short upstream ORFs in different sp ecies. Promoter activity of a fragment upstream of the cap site was shown b y transient expression in myoblasts and in vivo following intramuscular inj ection. It is tissue- and developmentally regulated. Analysis of promoter d eletions suggests the existence of negative regulatory elements in the prox imal region.