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PMID: 1846598 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The EMBO journal ·Vol. 10 ·No. 1 ·1991-01-00 ·Pages 59-69

Leroy P, Krust A, Zelent A, Mendelsohn C, Garnier JM, Kastner P, Dierich A, Chambon P

Abstract

Together with the previously described mouse retinoic acid receptor alpha-1 (mRAR-alpha 1, formerly mRAR-alpha 0), we have isolated and characterized here a total of seven mRAR-alpha cDNA isoforms (mRAR-alpha 1 to alpha 7). These isoforms are generated from mRAR-alpha 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-alpha 1 and alpha 2, 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-alpha 3 and alpha 4 cDNA isoforms remain open to their very 5' ends, which suggests that these two isoforms may also encode RAR-alpha s with unique A region amino acid sequences. The two predominant isoforms, mRAR-alpha 1 and alpha 2, 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-alpha 2, in contrast to that of the mRAR-alpha 1 isoform, was induced by retinoic acid (RA) in EC cells, thus suggesting the presence of two promoters in the 5' region of the mRAR-alpha gene, which differ in their response to RA. The conservation between mouse and human RAR-alpha 1 and alpha 2 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.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Carrier Proteins/biosynthesis,drug effects,genetics DNA/genetics,isolation & purification Exons Gene Library Genetic Variation Humans Mice Molecular Sequence Data Oligonucleotide Probes Polymerase Chain Reaction Promoter Regions, Genetic RNA Splicing RNA, Messenger/genetics Receptors, Retinoic Acid Sequence Homology, Nucleic Acid Tretinoin/pharmacology
Chemicals
Carrier Proteins Oligonucleotide Probes RNA, Messenger Receptors, Retinoic Acid Tretinoin DNA
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Leroy P
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire et de Génie Génétique de l'INSERM, Faculté de Médecine, Strasbourg, France.
Krust A
Zelent A
Mendelsohn C
Garnier J M
Kastner P
Dierich A
Chambon P
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1991-01-00
Pages
59-69
Language
English
Region
England
NLM ID
8208664
PMCID
PMC452611
Subset
IM
Grants
NIGMS NIH HHS · GM 13597 · United States
NIDDK NIH HHS · R01 DK061459-08 · United States
NIDDK NIH HHS · R01 DK061459-07S1 · United States
NIDDK NIH HHS · R01 DK061459-09 · United States
NIDDK NIH HHS · R01 DK061459 · United States
NIDDK NIH HHS · R56 DK082963-01 · United States
NIDDK NIH HHS · R01 DK061459-06 · United States
NIDDK NIH HHS · R56 DK082963 · United States
NIDDK NIH HHS · R01 DK061459-07 · United States
Databases
GENBANK
X56565, X56566, X56567, X56568, X56570, X56571, X56572, X57260, X57261, X57262
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