A GC-RICH DOMAIN WITH BIFUNCTIONAL EFFECTS ON MESSENGER-RNA AND PROTEIN-LEVELS - IMPLICATIONS FOR CONTROL OF TRANSFORMING GROWTH-FACTOR-BETA-1 EXPRESSION

作者：SCOTTO L; ASSOIAN RK

来源：Molecular and Cellular Biology, 1993, 13(6): 3588-3597.

Chimeric plasmids containing selected reporter coding domains and portions of the transforming growth factor beta1 (TGF-beta1) 3' untranslated region (UTR) were prepared and used to identify potential mechanisms involved in regulating the biosynthesis of TGF-beta1. Transient transfections with core and chimeric constructs containing the chloramphenicol acetyltransferase (CAT) reporter showed that steady-state CAT mRNA levels were decreased two- to threefold in response to the TGF-beta1 3' UTR. Interestingly, CAT activity was somewhat increased in the same transfectants. Thus, production of CAT protein per unit of mRNA was stimulated by the TGF-beta1 3' UTR (approximately fourfold in three cell lines of distinct lineage). The translation-stimulatory effect of the TGF-beta1 3' UTR suggested by these studies in vivo was confirmed in vitro by cell-free translation of core and chimeric transcripts containing the growth hormone coding domain. These studies showed that production of growth hormone was stimulated threefold by the TGF-beta1 3' UTR. A deletion analysis in vivo indicated that the GC-rich domain in the TGF-beta1 3' UTR was responsible for both the decrease in mRNA levels and stimulation of CAT activity-mRNA. We conclude that this GC-rich domain can have a bifunctional effect on overall protein expression. Moreover, the notable absence of this GC-rich domain in TGF-beta2, TGF-beta3, TGF-beta4, and TGF-beta5 indicates that expression of distinct TGF-beta family members can be differentially controlled in cells.

• 出版日期1993-6