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https://hdl.handle.net/10316/110049
Título: | Alpha-MSH regulates intergenic splicing of MC1R and TUBB3 in human melanocytes | Autor: | Dalziel, Martin Kolesnichenko, Marina Neves, Ricardo Pires das Iborra, Francisco Goding, Colin Furger, André |
Data: | Mar-2011 | Editora: | Oxford University Press | Projeto: | Wellcome Trust (081083/Z/06/Z) E.P.A. Cephalosporin Fund (C069) Skaggs Scholarship TSRI Pembroke College, BTP fellowship |
Título da revista, periódico, livro ou evento: | Nucleic Acids Research | Volume: | 39 | Número: | 6 | Resumo: | 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. | URI: | https://hdl.handle.net/10316/110049 | ISSN: | 1362-4962 0305-1048 |
DOI: | 10.1093/nar/gkq1125 | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais |
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α-MSH regulates intergenic splicing of MC1R and TUBB3 in human melanocytes.pdf | 3.79 MB | Adobe PDF | Ver/Abrir |
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