Multiple isoforms of the mouse retinoic acid receptor α are generated by alternative splicing and differential induction by retinoic acid

P. Leroy, A. Krust, A. Zelent, C. Mendelsohn, J. M. Garnier, P. Kastner, A. Dierich, P. Chambon

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Abstract

Together with the previously described mouse retinoic acid receptor alpha-1 (mRAR-α1, formerly mRAR-α0), we have isolated and characterized here a total of seven mRAR-α cDNA isoforms (mRAR-α1 to α7). These isoforms are generated from mRAR-α primary transcript(s) of a single gene by alternative splicing of at least eight different exons with the exon which encodes the amino acid sequence of their common B region. All of these isoforms differ in their 5'-untranslated regions (5'-UTRs) and, in the case of mRAR-α1 and α2, also in the sequences encoding the N-terminal A region which is known to be important for differential trans-activation by other members of the nuclear receptor superfamily. In addition, the sequences encoding the open reading frames (ORFs) of mRAR-α3 and α4 cDNA isoforms remain open to their very 5' ends, which suggests that these two isoforms may also encode RAR-αs with unique A region amino acid sequences. The two predominant isoforms, mRAR-α1 and α2, were found to be differentially expressed in mouse adult and fetal tissues, as well as in P19 and F9 embryonal carcinoma (EC) cell lines. Interestingly, the expression of mRAR-α2, in contrast to that of the mRAR-α1 isoform, was induced by retinoic acid (RA) in EC cells, thus suggesting the presence of two promoters in the 5' region of the mRAR-α gene, which differ in their response to RA. The conservation between mouse and human RAR-α1 and α2 cDNA isoform sequences, as seen by cross-hybridization in Southern blots or by DNA sequence analysis, together with their differential patterns of expression, strongly suggests that they perform specific functions during embryogenesis and in the adult.

Original languageEnglish (US)
Pages (from-to)59-69
Number of pages11
JournalEMBO Journal
Volume10
Issue number1
StatePublished - Jan 28 1991

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Keywords

  • 5'-UTR
  • EC cells
  • mouse RAR-α cDNA isoforms
  • mouse embryo
  • promoter

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Leroy, P., Krust, A., Zelent, A., Mendelsohn, C., Garnier, J. M., Kastner, P., Dierich, A., & Chambon, P. (1991). Multiple isoforms of the mouse retinoic acid receptor α are generated by alternative splicing and differential induction by retinoic acid. EMBO Journal, 10(1), 59-69.