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(Hypertension. 1996;28:810-817.)
© 1996 American Heart Association, Inc.

Articles

Translational Regulation of Angiotensin II Type 1A Receptor

Role of Upstream AUG Triplets

Yasukiyo Mori; Hiroaki Matsubara; Satoshi Murasawa; Kazuhisa Kijima; Katsuya Maruyama; Hiroyasu Tsukaguchi; Naohiko Okubo; Takao Hamakubo; Tadashi Inagami; Toshiji Iwasaka; Mitsuo Inada

the Department of Medicine II, Kansai Medical University, Osaka, Japan, and the Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tenn (T.H., T. Inagami).

The cDNA sequence of rat angiotensin II type 1A receptor (AT_1AR) shows that AT_1AR 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_1AR–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_1AR cDNA–transfected Cos-7 cells revealed that mutagenesis of the upstream AUG increased the AT_1AR protein up to 2.5-fold, although AT_1AR transcript levels showed no changes. The synthetic peptide corresponding to the sequence of the short open reading frame significantly suppressed the amount of AT_1AR 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_1AR 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_1AR transcripts has a certain role in the translation of AT_1AR protein.

Key Words: receptors, angiotensin II • molecular biology • muscle, smooth, vascular • genes • rats

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