title: Alternatively spliced human type 1 angiotensin II receptor mRNAs are translated at different efficiencies and encode two receptor isoforms.
abstract: The peptide hormone angiotensin II (AngII) plays a principal role in regulating blood pressure and fluid homeostasis. Most of its known effects are mediated by a guanine nucleotide-regulatory protein (G protein)-coupled receptor pharmacologically defined as the type-1 AngII receptor or AT1. Characterization of cDNA and genomic clones shows that the human AT1 gene contains five exons and encodes two receptor isoforms as a result of alternative splicing. Exon 5 contains the previously characterized open reading frame for AT1, and exons 1 to 3 are alternatively spliced upstream of it to generate several mRNA species, while transcripts containing exon 4 are of minor abundance. In an in vitro translation system, the presence of exon 1 was found to be extremely inhibitory to translation, probably because it can form a stable secondary structure at the RNA level. The alternatively spliced second exon also had a strong inhibitory effect on translation, presumably because it contains a minicistron commencing with an ATG in an optimal context for translation initiation. Exon 2 was similarly inhibitory to protein production in transfected cells, but exon 1 was found to enhance protein synthesis in this system. Transcripts containing exon 3 and 5, which comprise up to one-third of AT1 mRNAs in all tissues examined, encode a receptor with an amino-terminal extension of 32-35 amino acids. These transcripts were translated into a larger receptor isoform in vitro and produced a functional receptor with normal ligand binding and signaling properties in transfected cells.
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D010582:Bacteriophage lambda / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D018076:DNA, Complementary / Q000737:chemistry; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D011945:Receptors, Angiotensin / Q000235:genetics*; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D011945:Receptors, Angiotensin