Differentially expressed isoforms of the mouse retinoic acid receptor β are generated by usage of two promoters and alternative splicing

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

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Abstract

Using anchored PCR, three different cDNA isoforms of the mouse retinoic acid receptor β [mRAR-β1, mRAR-β2 (formerly mRAR-β0) and mRAR-β3], generated from the same gene by differential promoter usage and alternative splicing, were isolated. These three isoforms encode RAR proteins with different N-terminal A regions and identical B-F regions. The sequence encoding the first 59 amino acids of the mRAR-β3 A region is identical with the entire A region of mRAR-β1. However, the sequence of mRAR-β3 region A differs from that of mRAR-β1 by an additional 27 C-terminal amino acids encoded in an 81 nucleotide-long putative exon which is spliced in between the exons encoding the A and B regions of mRAR-β1. Both mRAR-β1 and β3 cDNAs differ entirely from mRAR-β2 in their 5'-untranslated (5'-UTR) and A region coding sequences. This N-terminal variability, in a region which was shown to be important for cell-type specific differential target gene trans-activation by other nuclear receptors, suggests that the three mRAR-β isoforms may be functionally distinct. The conservation of RAR-β isoform sequences from mouse to human, as seen by cross-hybridization on Southern blots or DNA sequence analysis, as well as their differential patterns of expression in various mouse tissues, corroborates this view. Additionally, the mRNA analysis data suggest that mRAR-β2, whose expression predominates in RA-treated embryonal carcinoma (EC) and embryonic stem (ES) cells, may be important during early stages of development. mRAR-β1 and β3, on the other hand, which are predominantly expressed in fetal and adult brain, may play some specific role in the development of the central nervous system.

Original languageEnglish (US)
Pages (from-to)71-81
Number of pages11
JournalEMBO Journal
Volume10
Issue number1
StatePublished - Jan 28 1991

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Keywords

  • 5'-UTR
  • EC cells
  • mouse RAR-β cDNA isoforms
  • mouse embryo
  • retinoic acid induction

ASJC Scopus subject areas

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

Cite this

Zelent, A., Mendelsohn, C., Kastner, P., Krust, A., Garnier, J. M., Ruffenach, F., Leroy, P., & Chambon, P. (1991). Differentially expressed isoforms of the mouse retinoic acid receptor β are generated by usage of two promoters and alternative splicing. EMBO Journal, 10(1), 71-81.