Combinatorial complexity of 5′ alternative acetylcholinesterase transcripts and protein products

Eran Meshorer, Debra Toiber, Dror Zurel, Iman Sahly, Amir Dori, Emanuela Cagnano, Letizia Schreiber, Dan Grisaru, François Tronche, Hermona Soreq*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


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.

Original languageAmerican English
Pages (from-to)29740-29751
Number of pages12
JournalJournal of Biological Chemistry
Issue number28
StatePublished - 9 Jul 2004


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