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Cell Growth & Differentiation, Vol 5, Issue 2 117-124, Copyright © 1994 by American Association of Cancer Research


ARTICLES

Analysis of transforming growth factor beta 1 messenger RNA degradation by the transcript-selective, 12-O-tetradecanoylphorbol-13-acetate-regulated ribonuclease system from U937 promonocytes

RE Wager, L Scotto and RK Assoian
Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032.

Transforming growth factor (TGF) beta 1 mRNA is selectively stabilized during 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced differentiation of U937 promonocytes. In previous studies (R. Wager and R. Assoian, Mol. Cell. Biol., 10: 5983-5990, 1990), we showed that this phenotype results from the action of a RNase system that (a) recognizes the transcript selectively and (b) is inhibited upon exposure of cells to TPA. The studies reported here were designed to localize domains of TGF-beta 1 mRNA required for recognition by this TPA-regulated, transcript-selective RNase system. By examining the degradation of several truncated TGF-beta 1 in vitro transcripts with U937 cell extracts, we show that the coding domain is sufficient to allow selective degradation of the mRNA and that this process is enhanced by either the 5' or 3' untranslated regions. The 5' and 3' untranslated regions of TGF-beta 1 mRNA are also required for TPA-mediated inhibition of the transcript-selective RNase system. In contrast, an analysis of the half-lives of the 2.1- and 1.8-kilobase TGF-beta 1 mRNAs showed that the first 270 bases, unique to the larger TGF-beta 1 mRNA, minimally affect degradation of the transcript. Finally, a survey of several transcripts showed that gamma-actin mRNA levels are also controlled by the TPA-regulated RNase system. The regulated decay of TGF-beta 1 mRNA may reflect the behavior of a class of transcripts subject to similar posttranscriptional controls on overall gene expression.





HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1994 by the American Association of Cancer Research.