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Title: Alpha-MSH regulates intergenic splicing of MC1R and TUBB3 in human melanocytes
Authors: Dalziel, Martin
Kolesnichenko, Marina
Neves, Ricardo Pires das 
Iborra, Francisco
Goding, Colin
Furger, André
Issue Date: Mar-2011
Publisher: Oxford University Press
Project: Wellcome Trust (081083/Z/06/Z) 
E.P.A. Cephalosporin Fund (C069) 
Skaggs Scholarship TSRI 
Pembroke College, BTP fellowship 
Serial title, monograph or event: Nucleic Acids Research
Volume: 39
Issue: 6
Abstract: Alternative splicing enables higher eukaryotes to increase their repertoire of proteins derived from a restricted number of genes. However, the possibility that functional diversity may also be augmented by splicing between adjacent genes has been largely neglected. Here, we show that the human melanocortin 1 receptor (MC1R) gene, a critical component of the facultative skin pigmentation system, has a highly complex and inefficient poly(A) site which is instrumental in allowing intergenic splicing between this locus and its immediate downstream neighbour tubulin-β-III (TUBB3). These transcripts, which produce two distinct protein isoforms localizing to the plasma membrane and the endoplasmic reticulum, seem to be restricted to humans as no detectable chimeric mRNA could be found in MC1R expressing mouse melanocytes. Significantly, treatment with the MC1R agonist α-MSH or activation of the stress response kinase p38-MAPK, both key molecules associated with ultraviolet radiation dermal insult and subsequent skin tanning, result in a shift in expression from MC1R in favour of chimeric MC1R-TUBB3 isoforms in cultured melanocytes. We propose that these chimeric proteins serve to equip melanocytes with novel cellular phenotypes required as part of the pigmentation response.
ISSN: 1362-4962
DOI: 10.1093/nar/gkq1125
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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