Post-transcriptional regulation of the cystic fibrosis gene in cardiac development and hypertrophy.
Eukaryotic gene expression, reflected in the amount of steady-state mRNA, is regulated at the post-transcriptional level. The 5'-untranslated regions (5'-UTRs) of some transcripts contain cis-acting elements, including upstream open reading frames (uORFs), that have been identified as being fundamental in modulating translation efficiency and mRNA stability. Previously, we demonstrated that uORFs present in the 5'-UTR of cystic fibrosis transmembrane conductance regular (CFTR) transcripts expressed in the heart were able to modulate translation efficiency of the main CFTR ORF. Here, we show that the same 5'-UTR elements are associated with the differential stability of the 5'-UTR compared to the main coding region of CFTR transcripts. Furthermore, these post-transcriptional mechanisms are important factors governing regulated CFTR expression in the heart, in response to developmental and pathophysiological stimuli.
Davies
Wayne L
WL
School of Biomedical Sciences, University of Queensland, Brisbane, Qld 4072, Australia.
Vandenberg
Jamie I
JI
Sayeed
Rana A
RA
Trezise
Ann E O
AE
D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D006332:Cardiomegaly / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D017931:DNA Primers; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D016133:Polymerase Chain Reaction; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits
D020121:5' Untranslated Regions; D017931:DNA Primers; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator