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Publication : Combinatorial complexity of 5' alternative acetylcholinesterase transcripts and protein products.

First Author  Meshorer E Year  2004
Journal  J Biol Chem Volume  279
Issue  28 Pages  29740-51
PubMed ID  15123727 Mgi Jnum  J:91689
Mgi Id  MGI:3050190 Doi  10.1074/jbc.M402752200
Citation  Meshorer E, et al. (2004) Combinatorial complexity of 5' alternative acetylcholinesterase transcripts and protein products. J Biol Chem 279(28):29740-51
abstractText  To explore the scope and significance of alternate promoter usage and its putative inter-relationship to alternative splicing, we searched expression sequence tags for the 5' region of acetylcholinesterase (ACHE) genes. Three and five novel first exons were identified in human and mouse ACHE genes, respectively. Reverse transcription-PCR and in situ hybridization validated most of the predicted transcripts, and sequence analyses of the corresponding genomic DNA regions suggest evolutionarily conserved promoters for each of the novel exons identified. Distinct tissue specificity and stress-related expression patterns of these exons predict combinatorial complexity with known 3' alternative AChE mRNA transcripts. Unexpectedly one of the 5' exons encodes an extended N terminus in-frame with the known AChE sequence, extending the increased complexity to the protein level. The resultant membrane variant(s), designated N-AChE, is developmentally regulated in human brain neurons and blood mononuclear cells. Alternative promoter usage combined with alternative splicing may thus lead to stress-dependent combinatorial complexity of AChE mRNA transcripts and their protein products.
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