Translational control elements in the major human transforming growth factor-beta 1 mRNA

Polysome analysis indicates that the major 2.4 kb transforming growth factor-beta 1 (TGF-beta 1) transcript is poorly translated, both in cultured cells, and in vivo in mouse liver. In contrast, the TGF-beta 2 transcripts are efficiently translated. The contribution of the 5'- and 3'-untranslated regions (UTRs) to the translational inhibition of the full-length TGF-beta 1 transcript was studied by deletion analysis. Despite their high G + C content, both UTRs stimulated translation in vitro. However, polysome analysis of synthetic TGF-beta 1 mRNAs transfected into MCF-7 cells suggests that the cell contains a limited pool of trans-acting factors that interact with the 5'UTR to make it inhibitory in vivo. Further deletion analysis in vitro revealed multiple stimulatory and inhibitory regions in the 5'UTR. This has important implications for the translatability of the naturally occurring shorter TGF-beta 1 transcripts and provides a framework for higher resolution mapping studies. Overall, the poor translational efficiency of the major TGF-beta 1 mRNA in vivo appears to be due to a combination of poor initiation sequence context, and inhibitory interactions of limiting transacting factors with cis-inhibitory elements embedded in an otherwise stimulatory 5'UTR.