Post-transcriptional regulation of the human transforming growth factor-beta 1 gene.
Since many lines of evidence suggest that expression of the transforming growth factor-beta 1 (TGF-beta 1) gene may be regulated post-transcriptionally, we examined the effect of the 5'-untranslated region (UTR) of this gene on TGF-beta 1 expression. For this purpose, fragments of the 840-nucleotide highly GC-rich TGF-beta 1 5'-UTR were inserted into the 5'-UTR of the structural gene for human growth hormone driven by the simian virus 40 early promoter. A portion of the 5'-UTR of TGF-beta 1 mRNA spanning the sequences from +11 to +147 was shown to inhibit growth hormone expression by as much as 22-fold. This effect was cell-specific; growth hormone production was inhibited in PC-3 human prostate adenocarcinoma and A-549 human lung adenocarcinoma cells, while no effect was seen in rat pheochromocytoma PC12 cells, which show efficient translation of endogenous TGF-beta 1 mRNA. Computer analysis showed that this region of the 5'-UTR contained a stable secondary stem-loop structure spanning sequences +49 to +76. This stem-loop region alone is sufficient to inhibit expression of the growth hormone gene, suggesting that it plays an important role in post-transcriptional regulation of TGF-beta 1 gene expression.
Kim
S J
SJ
Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Park
K
K
Koeller
D
D
Kim
K Y
KY
Wakefield
L M
LM
Sporn
M B
MB
Roberts
A B
AB
D000818:Animals; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D016716:PC12 Cells; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013006:Growth Hormone; D015500:Chloramphenicol O-Acetyltransferase