TY - JOUR
T1 - Modulated splicing-associated gene expression in P19 cells expressing distinct acetylcholinesterase splice variants.
AU - Ben-Ari, Shani
AU - Toiber, Debra
AU - Sas, Aldema S.
AU - Soreq, Hermona
AU - Ben-Shaul, Yoram
PY - 2006/4
Y1 - 2006/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33646847625&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2006.03725.x
DO - 10.1111/j.1471-4159.2006.03725.x
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C2 - 16635247
AN - SCOPUS:33646847625
SN - 0022-3042
VL - 97 Suppl 1
SP - 24
EP - 34
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
ER -