An alternative transcript of the rat renin gene can result in a truncated prorenin that is transported into adrenal mitochondria

Characterization of the local renin-angiotensin system in the rat adrenal z ona glomerulosa indicated a dual targeting of renin both to the secretory p athway and mitochondria. To investigate the transport of renin into mitocho ndria, we constructed a series of amino-terminal deletion variants of prepr orenin. One of these variants, lacking the complete signal sequence for the endoplasmic reticulum and 10 amino acids of the profragment, was transport ed efficiently into isolated mitochondria. The transport was further shown to be dependent on mitochondrial membrane potential and ATP synthesis. Anal ysis of adrenal RNA revealed the existence of 2 renin transcripts. While on e of the transcripts corresponds to the known full-length transcript, the o ther one lacks exon 1; instead, exon 2 is preceded by a domain of 80 nucleo tides originating from intron 1. This domain, as well as the following regi on of intron 1 being excised, shows all essential sequence elements definin g an additional, so-far-unknown exon. The second mRNA possibly derives from an additional transcription start in intron 1 and an alternative splicing process. Translation of this mRNA could result in a truncated prorenin repr esenting a cytosolic form of renin, which is required for transport into mi tochondria. This truncated prorenin corresponds exactly to the deletion var iant being imported into mitochondria in vitro.