Identification of three human renin mRNA isoforms from alternative tissue-specific transcriptional initiation. Physiol Genomics 2000 Jun 29;3(1):25-31
Date
10/04/2000Pubmed ID
11015597DOI
10.1152/physiolgenomics.2000.3.1.25Scopus ID
2-s2.0-0034729573 (requires institutional sign-in at Scopus site) 94 CitationsAbstract
We have reported that mice transgenic for 140- and 160-kb P1 phage artificial chromosomes (PACs) containing the human renin gene express the gene in a highly tissue-restricted and regulated manner. Herein, we demonstrate that the transgene is also expressed appropriately throughout development. In the course of this investigation, we identified the existence of three transcriptional isoforms of human renin mRNA derived from the utilization of alternative transcription start sites. The first isoform is the kidney-specific isoform, which utilizes the classic renin promoter. The second is a brain-specific isoform, which when previously identified in rats and mice was due to a transcription initiation site within intron A. However, the start site in the human gene resides approximately 1,325 bp upstream of the classic promoter and encodes a new exon 1 (termed exon 1b) that splices directly to exon 2. The third isoform is lung specific and is due to transcriptional initiation 79 bp directly upstream of exon 2, fusing additional DNA within intron A (termed exon 1c) directly to exon 2 without splicing. Importantly, the alternative first exons observed in the PAC transgenic mice were identical to those used to transcribe renin in human fetal kidney, brain, and lung, suggesting these sites are bona fide isoforms of human renin mRNA and not artifacts of transgenesis. Moreover, the subtle differences in tissue-specific transcriptional initiation observed in the renin gene of rats and humans can be faithfully and accurately emulated in a transgenic model.
Author List
Sinn PL, Sigmund CDAuthor
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Alternative SplicingAnimals
Brain
Codon, Initiator
Female
Gene Dosage
Heart
Humans
Intestines
Liver
Lung
Male
Mice
Mice, Transgenic
Myocardium
Organ Specificity
Protein Isoforms
RNA, Messenger
Renin
Transcription, Genetic
Transgenes
