title: Combinatorial complexity of 5' alternative acetylcholinesterase transcripts and protein products.
abstract: 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.
authors.affiliation: Department of Biological Chemistry and the Israel Center of Neuronal Computation, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Meshorer
authors.forename: Debra
authors.initials: D
authors.lastname: Toiber
authors.forename: Dror
authors.initials: D
authors.lastname: Zurel
authors.forename: Iman
authors.initials: I
authors.lastname: Sahly
authors.forename: Amir
authors.initials: A
authors.lastname: Dori
authors.forename: Emanuela
authors.initials: E
authors.lastname: Cagnano
authors.forename: Letizia
authors.initials: L
authors.lastname: Schreiber
authors.forename: Dan
authors.initials: D
authors.lastname: Grisaru
authors.forename: François
authors.initials: F
authors.lastname: Tronche
authors.forename: Hermona
authors.initials: H
authors.lastname: Soreq
mesh_terms: D020121:5' Untranslated Regions; D000110:Acetylcholinesterase / Q000235:genetics* / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000378:metabolism; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005091:Exons; D020224:Expressed Sequence Tags; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological; D014018:Tissue Distribution
chemical_list: D020121:5' Untranslated Regions; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D000110:Acetylcholinesterase