title: Multiple non-coding exons and alternative splicing in the mouse Mas protooncogene.
abstract: The Mas protooncogene encodes a G protein-coupled receptor with the common seven transmembrane domains, expressed mainly in the testis and brain. We provided evidence that Mas is a functional angiotensin-(1-7) receptor and can interact with the angiotensin II type 1 (AT1) receptor. The gene is transcriptionally regulated during development in the brain and testis, but its structure was unresolved. In this study we used 5'- and 3'-RACE, RT-PCR, and RNase-protection assays to elucidate the complete Mas gene structure and organization. We identified 12 exons in the mouse Mas gene with 11 in the 5' untranslated mRNA, which can be alternatively spliced. We also showed that Mas transcription can start from 4 tissue-specific promoters, whereby testis-specific Mas mRNA is transcribed from two upstream promoters, and the expression of Mas in the brain starts from two downstream promoters. Alternative splicing and multiple promoter usage result in at least 12 Mas transcripts in which different 5' untranslated regions are fused to a common coding sequence. Moreover, termination of Mas mRNA is regulated by two different polyadenylation signals. The gene spans approximately 27 kb, and the longest detected mRNA contains 2,451 bp. Thus, our results characterize the Mas protooncogene as the gene with the most complex gene structure of all described members of the gene family coding for G protein-coupled receptors.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10, 13092 Berlin-Buch, Germany; Federal University of Minas Gerais (UFMG), ICB, 6627 Belo Horizonte, MG, Brasil.
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.affiliation: Centre for Perinatal Medicine, University Medical Centre Leipzig, Liebigstraße 20a, 04103 Leipzig, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Böhme
authors.affiliation: Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10, 13092 Berlin-Buch, Germany; Federal University of Minas Gerais (UFMG), ICB, 6627 Belo Horizonte, MG, Brasil; Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.affiliation: Centre for Perinatal Medicine, University Medical Centre Leipzig, Liebigstraße 20a, 04103 Leipzig, Germany; Department of Pharmacology and Therapeutics, 2nd Floor, Western Road, University College Cork, Cork, Ireland. Electronic address: t.walther@ucc.ie.
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
mesh_terms: D020413:3' Untranslated Regions; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D005091:Exons; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D024363:Transcription Initiation Site
chemical_list: D020413:3' Untranslated Regions; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled
keywords: G protein-coupled receptor; Mas gene structure; Tissue-specific promoter