PMID- 8361501 OWN - NLM STAT- MEDLINE DCOM- 19930924 LR - 20131121 IS - 0888-8809 (Print) IS - 0888-8809 (Linking) VI - 7 IP - 6 DP - 1993 Jun TI - An element of the transforming growth factor-beta 1 5'-untranslated region represses translation and specifically binds a cytosolic factor. PG - 759-66 AB - 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. FAU - Romeo, D S AU - Romeo DS AD - National Cancer Institute, Laboratory of Chemoprevention, Bethesda, Maryland 20892. FAU - Park, K AU - Park K FAU - Roberts, A B AU - Roberts AB FAU - Sporn, M B AU - Sporn MB FAU - Kim, S J AU - Kim SJ LA - eng PT - Journal Article PL - United States TA - Mol Endocrinol JT - Molecular endocrinology (Baltimore, Md.) JID - 8801431 RN - 0 (RNA Probes) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) RN - 1CC1JFE158 (Dactinomycin) RN - 9002-72-6 (Growth Hormone) RN - EC 3.1.- (Ribonucleases) SB - IM MH - Animals MH - Blotting, Northern MH - Cell Line MH - Cytosol/*metabolism MH - Dactinomycin/pharmacology MH - Gene Expression MH - Growth Hormone/genetics MH - Humans MH - Mice MH - Muscles/metabolism MH - Nucleic Acid Hybridization MH - Protein Binding MH - Protein Biosynthesis/*drug effects MH - RNA Probes MH - RNA, Messenger/genetics/metabolism/*pharmacology MH - Ribonucleases/metabolism MH - Transfection MH - Transforming Growth Factor beta/*genetics MH - Ultraviolet Rays EDAT- 1993/06/01 00:00 MHDA- 1993/06/01 00:01 CRDT- 1993/06/01 00:00 PHST- 1993/06/01 00:00 [pubmed] PHST- 1993/06/01 00:01 [medline] PHST- 1993/06/01 00:00 [entrez] AID - 10.1210/mend.7.6.8361501 [doi] PST - ppublish SO - Mol Endocrinol. 1993 Jun;7(6):759-66. doi: 10.1210/mend.7.6.8361501.