Distinct renin isoforms generated by tissue-specific transcription initiation and alternative splicing
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
The aspartyl protease renin catalyzes the initial and rate-limiting step in the formation of the biologically active peptide angiotensin II. It is mainly synthesized in the kidney as a preprohormone and secreted via constitutive and regulated pathways. We identified a novel transcript of the rat renin gene, renin b, characterized by the presence of an alternative first exon (exon 1b) that is spliced to exon 2 of the known transcript, termed renin a. We demonstrated that renin b is exclusively expressed in the brain. In contrast, renin a was not expressed in the brain. Using primer extension assays, we mapped the transcriptional start site of this novel mRNA within intron 1 of the rat genomic sequence, suggesting the presence of a brain-specific promoter within intron 1. The presence of a brain-specific renin isoform is evolutionally conserved, as demonstrated by the finding of renin b isoforms in mice and humans. The predicted protein renin b lacks the prefragment as well as a significant portion of the profragment and is therefore predicted not to be a secreted protein, unlike the classically described isoform renin a. As shown by in vitro translation of full-length renin b mRNA in the presence of microsomal membranes, renin b was not targeted into the endoplasmatic reticulum and remained intracellularly in transiently transfected AtT-20 cells. These findings provide evidence for a novel pathway of intracellular angiotensin generation that occurs exclusively in the brain.
Details
Original language | English |
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Pages (from-to) | 240-246 |
Number of pages | 7 |
Journal | Circulation research |
Volume | 84 |
Issue number | 2 |
Publication status | Published - 5 Feb 1999 |
Peer-reviewed | Yes |
External IDs
PubMed | 9933256 |
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Keywords
ASJC Scopus subject areas
Keywords
- Alternative splicing, Brain, Gene expression, Renin, Renin-angiotensin system