Tissue-Specific Expression of a Rat Renin Transcript Lacking the Coding Sequence for the Prefragment and Its Stimulation by Myocardial Infarction*

Abstract

An alternative transcript of the rat renin gene was recently characterized in the adrenal gland, in addition to the known messenger RNA (mRNA) coding for preprorenin. In the alternative transcript, exon 1 is replaced by exon 1A, a domain originating in intron 1. The reading frame of this mRNA, termed exon 1A-renin transcript, codes for a truncated prorenin that presumably remains intracellular, in contrast to preprorenin, which is targeted to the secretory pathway by its prefragment. We here demonstrate the tissue-specific regulation of expression of both transcripts by RT and PCR. In many tissues both transcripts are present, for example in the adrenal gland, spleen, liver, and hypothalamus. In some organs, however, only one of the renin mRNAs is found. In the kidney only the full-length mRNA coding for preprorenin is detected. In the heart exclusively the exon 1A-mRNA is expressed, but not the preprorenin transcript. After myocardial infarction, which is known to activate the intracardiac renin-angiotensin system, expression of exon 1A-renin mRNA in the left ventricle was stimulated about 4-fold, compared with that in sham-operated animals, whereas no mRNA corresponding to preprorenin was detectable. These findings may have implications for the current concepts of local extrarenal renin-angiotensin systems, as they provide the molecular basis for a possible intracellular function of renin and exclude a role for locally produced secretory renin in the heart.