Premium
Transforming growth factor‐β1: There is regulation beyond transcription
Author(s) -
Brenner David A.
Publication year - 1993
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840170128
Subject(s) - untranslated region , biology , transforming growth factor , gene expression , messenger rna , gene , three prime untranslated region , microbiology and biotechnology , post transcriptional regulation , regulation of gene expression , cell growth , cancer research , genetics
Since many lines of evidence suggest that expression of the transforming growth factor‐β1 (TGF‐β1) gene may be regulated post‐transcriptionally, we examined the effect of the 5′‐untranslated region (UTR) of this gene on TGF‐β1 expression. For this purpose, fragments of the 840‐nucleotide highly GC‐rich TGF‐β1 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‐β1 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‐β1 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‐β1 gene expression.