Alternative splicing of CRH-R1 receptors in human and mouse skin: identification of new variants and their differential expression.
We identified four new isoforms of human CRH-R1 (e-h) and three of mouse (mCRH-R1c, e, and f). In all new forms exon 6 was missing. Human CRH-R1e was characterized by the deletion of exons 3 and 4; exon 12 from CRH-R1f; exon 11, 27 base pairs (bp) of exon 10 and 28 bp of exon 12 from CRH-R1g and CRH-R1h by the addition of a cryptic exon. In mouse CRH-R1c exon 3 was spliced out; in mCRH-R1e exons 3 and 4 and in mCRH-R1f exon 11 were spliced from mRNA. CRH-R1 was expressed in all skin specimens in patterns dependent on the cell type, physiological status, and presence of pathology. CRH-R1a, the most prevalent form, was detected in almost all samples. Ultraviolet radiation (UV) changed the splicing pattern and induced or increased expression of CRH-R1a in cultured skin cells. Continuing UV treatment of succeeding generations of cells resulted in a progressive increase in the number of CRH-R1 isoforms, which suggests that receptor heterogeneity might favor cell survival. TPA (phorbol 12-myristate 13-acetate), forskolin, dbcAMP (N6, 2'-O-dibutyryladenosine 3':5'-cyclic monophospate sodium), and IBMX (3-isobutyl-1-methylxanthine) also changed the splicing pattern. We suggest that a polymorphism of CRH-R1 expression is related to anatomic location, skin physiological or pathologic status, specific cell type, and external stress (UV), and that cAMP-dependent pathways and TPA may regulate CRH-R1.
Pisarchik
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Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Slominski
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D017398:Alternative Splicing; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D000099052:CRF Receptor, Type 1
D020033:Protein Isoforms; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D005576:Colforsin; D000099052:CRF Receptor, Type 1; D003994:Bucladesine; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine