Molecular Endocrinology, Vol 7, 759-766, Copyright © 1993 by Endocrine Society

ARTICLES

An element of the transforming growth factor-beta 1 5'-untranslated region represses translation and specifically binds a cytosolic factor

DS Romeo, K Park, AB Roberts, MB Sporn and SJ Kim
National Cancer Institute, Laboratory of Chemoprevention, Bethesda, Maryland 20892.

In many cell types, there is a discrepancy between transforming growth factor-beta 1 (TGF-beta 1) mRNA and TGF-beta 1 protein, suggesting that expression of TGF-beta 1 is regulated posttranscriptionally. We have previously shown that a 137-nucleotide (nt) region of the TGF-beta 1 5'- untranslated region (UTR) potently inhibits the expression of a heterologous reporter gene, suggesting a role for this region in the posttranscriptional inhibition of TGF-beta 1 expression. To study the mechanism of inhibition, a chimeric plasmid containing this region of the TGF-beta 1 5'-UTR and the reading frame of the human GH gene was stably transfected into C2C12 myoblastic cells. Our results show that the TGF-beta 1 5'-UTR inhibits GH expression by inhibiting GH mRNA translation. In vitro gel retardation and cross-linking assays using a radiolabelled RNA probe transcribed from this region of the TGF-beta 1 5'-UTR demonstrate the specific binding of a cytosolic factor. Deletion of a potential stem-loop-forming region abolishes binding of this factor and partially restores GH production. These results suggest that posttranscriptional inhibition of TGF-beta 1 expression is at the level of mRNA translation and that a cytosolic factor may regulate TGF-beta 1 mRNA translation.

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