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.