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

K. M. Curnow, L. Pascoe, E. Davies, P. C. White, P. Corvol, E. Clauser

Research output: Contribution to journalArticle

69 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1250-1262
Number of pages13
JournalMolecular Endocrinology
Volume9
Issue number9
StatePublished - 1995

Fingerprint

Angiotensin Type 1 Receptor
Exons
Protein Isoforms
Messenger RNA
Peptide Hormones
Alternative Splicing
GTP-Binding Proteins
Angiotensin II
Open Reading Frames
Proteins
Homeostasis
Complementary DNA
Clone Cells
RNA
Blood Pressure
Ligands
Amino Acids

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Alternatively spliced human type 1 angiotensin II receptor mRNAs are translated at different efficiencies and encode two receptor isoforms. / Curnow, K. M.; Pascoe, L.; Davies, E.; White, P. C.; Corvol, P.; Clauser, E.

In: Molecular Endocrinology, Vol. 9, No. 9, 1995, p. 1250-1262.

Research output: Contribution to journalArticle

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AU - Davies, E.

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AU - Corvol, P.

AU - Clauser, E.

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