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Papers In Press, published online ahead of print May 6, 2004
Biological Chemistry, Hebrew University, Jerusalem 91904
Corresponding Author: soreq{at}cc.huji.ac.il
To explore the scope and significance of alternate promoter usage and its putative interrelationship to alternative splicing, we searched EST sequences for the 5’ region of acetylcholinesterase (ACHE) genes. Three and five novel first exons were identified in human and mouse ACHE genes, respectively. RT-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, are 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.
J. Biol. Chem, 10.1074/jbc.M402752200
Submitted on March 11, 2004
Revised on April 26, 2004
Accepted on April 28, 2004
Combinatorial complexity of 5' alternative ACHE transcripts and protein products
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