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.
Abdulrazzak
H
H
Department of Anatomy and Developmental Biology, Division of Basic Medical Sciences, Royal Free and University College Medical School, London, NW3 2PF, United Kingdom.
Noro
N
N
Simons
J P
JP
Goldspink
G
G
Barnard
E A
EA
Górecki
D C
DC
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