Identification of a GA-rich sequence as a protein-binding site in the 3'-untranslated region of chicken elastin mRNA with a potential role in the developmental regulation of elastin mRNA stability.
Synthesis of aortic elastin peaks in the perinatal period and then is strongly down-regulated with postnatal development and growth. Decreased stability of elastin mRNA contributes to this developmental decrease in chick aortic elastin production. We have previously shown that destabilization of elastin mRNA is correlated with decreased binding of cytosolic protein(s) to a large, GC-rich region of secondary structure in the 3'-untranslated region (3'-UTR) of elastin mRNA. In this study, using gel migration shift assays, deletion constructs, and antisense competition assays, we identify a major protein-binding site in the 3'-UTR of elastin as a GA-rich sequence (UGGGGGGAGGGAGGGAGGGA), which we have designated the G3A motif. This motif is present in the 3'-UTR of elastin from several species. Binding proteins are present in both nuclear and cytoplasmic extracts, and their abundance is associated with tissues producing elastin and correlated with circumstances in which elastin mRNA is stable. These results suggest that the conserved GA-rich sequence of the elastin 3'-UTR is an important element in the regulation of stability of the elastin mRNA.
Hew
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Y
Cardiovascular Research Program, Research Institute, Hospital for Sick Children and Departments of Biochemistry and of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada M5G 1X8.
Lau
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C
Grzelczak
Z
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Keeley
F W
FW
D020413:3' Untranslated Regions / Q000737:chemistry / Q000235:genetics*; D000225:Adenine; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002417:Cattle; D002645:Chickens; D018900:Dinucleotide Repeats; D004549:Elastin / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006147:Guanine; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics; D051381:Rats; D016415:Sequence Alignment; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D012756:Sheep
D020413:3' Untranslated Regions; D012333:RNA, Messenger; D006147:Guanine; D004549:Elastin; D000225:Adenine