Open AccessDifferential expression of human nicotinic acetylcholine receptor α subunit variants in muscle and non-muscle tissues
Author(s) -
Sohel Talib,
Thomas B. Okarma,
Jane Lebkowski
Publication year - 1993
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/21.2.233
Subject(s) - biology , exon , alternative splicing , skeletal muscle , rna splicing , complementary dna , genetics , nicotinic acetylcholine receptor , microbiology and biotechnology , protein subunit , acetylcholine receptor , gene , rna , receptor , anatomy
The nicotinic acetylcholine receptor (nAChR) is an oligomeric transmembrane glycoprotein consisting of four homologous subunits in stoichiometry of alpha 2, beta (gamma or epsilon). Recently the presence of a novel exon (P3A) in human alpha AChR gene has been reported. Two variants of the human alpha subunit arise from alternate RNA splicing, one with and one without the P3A exon. However, the evolutionary origin of the P3A exon and the regulation of the expression of the two variants in human muscle and non-human tissues is currently unknown. Examination of genomic DNA from various species shows that the P3A exon sequence is present only in hominoids, old world and new world primates species and is absent in the muscle cDNA or genomic DNA from rat, mouse or dog, indicating that P3A exon is evolutionary conserved for at least 50 million years. The P3A+ variant of alpha subunit was found to be constitutively expressed in skeletal muscle, brain, heart, kidney, liver, lung and thymus, while P3A-variant was differentially expressed only in skeletal muscle. Thus it appears that the P3A+ variant is generated by 'default' selection by the splicing machinery, while expression of the P3A- variant is regulated by tissue-specific factors in the skeletal muscle. Mechanisms regulating differential expression of the alpha subunit variants may be pertinent to the pathophysiology of myasthenia gravis.