Translational Regulation of Angiotensin II Type 1A Receptor

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Abstract
The cDNA sequence of rat angiotensin II type 1A receptor (AT 1A R) shows that AT 1A R transcripts have AUG triplets in the 5′-leader region that may begin a short open reading frame encoding an 11–amino acid peptide. In this study, the mutational inactivation of the start codon of the short open reading frame in AT 1A R–chloramphenicol acetyltransferase (CAT) reporter gene constructs resulted in a 2.6-fold increase in CAT activity, whereas CAT transcript levels were not affected. Furthermore, experiments with rat AT 1A R cDNA–transfected Cos-7 cells revealed that mutagenesis of the upstream AUG increased the AT 1A R protein up to 2.5-fold, although AT 1A R transcript levels showed no changes. The synthetic peptide corresponding to the sequence of the short open reading frame significantly suppressed the amount of AT 1A R product in the in vitro translation system. The inhibiting effect of the short open reading frame appears to operate at least in part at the level of translation initiation, because polysome analysis with transfected Cos-7 cells showed that mutagenesis of the upstream AUG resulted in a shift of AT 1A R mRNA distribution from a smaller to larger fraction of polysomes. Taken together, these results show that the upstream AUG inhibits translational regulation, suggesting that the short open reading frame in the 5′-leader region of AT 1A R transcripts has a certain role in the translation of AT 1A R protein.