Alternative splicing of CRH-R1 receptors in human and mouse skin: identification of new variants and their differential expression

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
A Pisarchik, Andrzej Slominski

Abstract

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 anat...Continue Reading

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