title: Modulated splicing-associated gene expression in P19 cells expressing distinct acetylcholinesterase splice variants.
abstract: Alternative splicing configurations and acetylcholinesterase (AChE) gene expression are both modified in neurons under stress. However, it is unclear if these phenomena are functionally interrelated. Using a home-made spotted microarray focused on splicing-associated transcripts, we tested the effects of excess 3' splice variants of human AChE on splicing-related gene expression in semi-differentiated neuronal P19 cells. Of the tested transcripts, 17.3% and 20.2% showed modified expression levels (log2 of the ratio<-0.3 or>0.3) in transfected P19 cells overexpressing the stress-inducible AChE-R variant or the synaptic AChE-S protein, respectively. Multiple transcripts encoding serine-arginine rich (SR) and SR-related splicing regulators were suppressed in cells expressing either of these variants, whereas the gene groups including splicing-related helicases and transcripts involved in apoptosis displayed variant-specific changes. Our findings are compatible with the assumption that both neuronal overexpression and alternative splicing of pre-AChE mRNA may be causally involved in initiating global changes in neuronal alternative splicing, causing subsequent modifications in the expression patterns of numerous target genes.
authors.affiliation: Department of Biological Chemistry and Israel Center for Neuronal Computation, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Shani
authors.initials: S
authors.lastname: Ben-Ari
authors.forename: Debra
authors.initials: D
authors.lastname: Toiber
authors.forename: Aldema S
authors.initials: AS
authors.lastname: Sas
authors.forename: Hermona
authors.initials: H
authors.lastname: Soreq
authors.forename: Yoram
authors.initials: Y
authors.lastname: Ben-Shaul
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics*; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D004622:Embryo, Mammalian; D004792:Enzyme Precursors / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017381:Spliceosomes / Q000235:genetics; D014162:Transfection; D050494:Vesicular Acetylcholine Transport Proteins / Q000235:genetics
chemical_list: D004792:Enzyme Precursors; D012333:RNA, Messenger; D050494:Vesicular Acetylcholine Transport Proteins; C087728:SRPK1 protein, human; D017346:Protein Serine-Threonine Kinases; D000110:Acetylcholinesterase