Alternatively spliced human type 1 angiotensin II receptor mRNAs are translated at different efficiencies and encode two receptor isoforms

Mol Endocrinol. 1995 Sep;9(9):1250-62. doi: 10.1210/mend.9.9.7491117.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing*
  • Amino Acid Sequence
  • Bacteriophage lambda / genetics
  • Base Sequence
  • Binding Sites
  • DNA, Complementary / chemistry
  • Exons
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Open Reading Frames
  • Protein Biosynthesis*
  • RNA, Messenger / analysis
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics*
  • Receptors, Angiotensin / genetics*
  • Tissue Distribution
  • Transcription, Genetic
  • Transfection


  • DNA, Complementary
  • RNA, Messenger
  • Receptors, Angiotensin

Associated data

  • GENBANK/S80189
  • GENBANK/S80190
  • GENBANK/S80192
  • GENBANK/S80194
  • GENBANK/S80239