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Volume 272, Number 7, Issue of February 14, 1997 pp. 4050-4057
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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Role of Gene Overlap in the Regulation of mRNA Translation for Mitochondrial Cytochrome P-450c27/25 in the Rat

(Received for publication, February 21, 1996, and in revised form, May 17, 1996)

From the Drug Liver Unit, Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140

Previously published results have revealed sequence complementarity between the 5-terminal regions of mRNAs for hepatic mitochondrial cytochrome P-450c27/ 25 (c27/25) and serine protease inhibitors (SPI) and predicted a role for this sequence overlap in both the regulation of c27/25 mRNA transcription and translation. The possibility that c27/25 mRNA forms an RNA duplex with complementary sequences of SPI mRNAs in vivo was demonstrated in the rat liver and COS-1 cells cotransfected with c27/25 and SPI2.1 plasmids. Quantitative evaluation of RNA duplex in COS-1 cells revealed that most of the c27/25 mRNA exists in duplex form when SPI2.1 mRNA was present at 5-10-fold that of c27/25 mRNA, a ratio comparable to that observed between these two RNAs in the liver. In cotransfected COS-1 cells with the same ratio of mRNAs, highly significant inhibition of the c27/25 mRNA translation (66-75%) was observed, while its transcription remained unaffected. The partial inhibition of c27/25 mRNA translation, even when most of it exists in duplex form, suggests that RNA duplex is undergoing some type of cytoplasmic processing to disengage c27/25 mRNA and make it available for translation. These results imply that abundant endogenous SPI RNAs are able to regulate the c27/25 gene expression.

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