Combinatorial complexity of 5' alternative acetylcholinesterase transcripts and protein products

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 ge...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-07, Vol.279 (28), p.29740-29751
Main Authors: Meshorer, Eran, Toiber, Debra, Zurel, Dror, Sahly, Iman, Dori, Amir, Cagnano, Emanuela, Schreiber, Letizia, Grisaru, Dan, Tronche, François, Soreq, Hermona
Format: Article
Language:English
Subjects:
5' Untranslated Regions
Acetylcholinesterase - genetics
Acetylcholinesterase - metabolism
Alternative Splicing
Animals
Base Sequence
Brain - cytology
Brain - metabolism
Embryo, Mammalian - anatomy & histology
Embryo, Mammalian - physiology
Exons
Expressed Sequence Tags
Humans
In Situ Hybridization, Fluorescence
Isoenzymes - genetics
Isoenzymes - metabolism
Mice
Molecular Sequence Data
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Promoter Regions, Genetic
Receptors, Glucocorticoid - genetics
Receptors, Glucocorticoid - metabolism
RNA, Messenger - metabolism
Stress, Psychological
Tissue Distribution
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.m402752200