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 and mRNAs in different species revealed strong sequence conservation but functional 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 upstream. Despite sequence homology, significant tissue- and species-specific structural diversity in the P-type 5'-ends exists, including alternative splicing within the 5'-untranslated region combined with alternative splicing 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 species. Promoter activity of a fragment upstream of the cap site was shown by transient expression in myoblasts and in vivo following intramuscular injection. It is tissue- and developmentally regulated. Analysis of promoter deletions suggests the existence of negative regulatory elements in the proximal region.
Department of Anatomy and Developmental Biology, Division of Basic Medical Sciences, Royal Free and University College Medical School, London, NW3 2PF, United Kingdom.
H
H
Abdulrazzak
N
N
Noro
J P
JP
Simons
G
G
Goldspink
E A
EA
Barnard
D C
DC
Górecki
D020121:5' Untranslated Regions / Q000235:genetics; D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D017124:Conserved Sequence; D016189:Dystrophin / Q000235:genetics*; D019143:Evolution, Molecular; D014644:Genetic Variation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D013045:Species Specificity; D014158:Transcription, Genetic / Q000235:genetics
D020121:5' Untranslated Regions; D016189:Dystrophin