Comment[ArrayExpressAccession]	E-GEOD-35113
Public Release Date	2012-01-17							
Investigation Title	Genome-wide analysis of gene expression and nuclear/cytoplasmic distribution by compound 1 treatment [293T_NS1-1]							
Comment[Submitted Name]	Genome-wide analysis of gene expression and nuclear/cytoplasmic distribution by compound 1 treatment [293T_NS1-1]
Experiment Description	Analysis of cellular response to DHODH inhibition at gene expression and nuclear/cytoplasmic distribution level. The NS1 protein of influenza virus is a major virulence factor essential for virus replication as it re-directs the host cell to promote viral protein expression. NS1 inhibits cellular mRNA processing and export, down-regulating host gene expression and enhancing viral gene expression. We report here the identification of a non-toxic quinoline carboxylic acid that reverts the inhibition of mRNA nuclear export by NS1, in the absence or presence of virus. This quinoline carboxylic acid directly inhibited dihydroorotate dehydrogenase (DHODH), a host enzyme required for *de novo* pyrimidine biosynthesis, and partially reduced pyrimidine levels. This effect induced NXF1 expression, which promoted mRNA nuclear export in the presence of NS1. The release of NS1-mediated mRNA export block by DHODH inhibition also occurred in the presence of VSV M protein, another viral inhibitor of mRNA export. This reversal of mRNA export block allowed expression of antiviral factors. Thus, pyrimidines play a necessary role in the inhibition of mRNA nuclear export by virulence factors. Five million 293T cells were non-transfected or transfected with 6ug of pCAGGS-NS1 for 16h. Then, cells were untreated or treated with compound 1(5uM) for 24h. RNA from total cell extracts or from nuclear or cytoplasmic fractions were obtained							
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Term Source File	http://www.ebi.ac.uk/efo/efo.owl							
Person Last Name	zhang	Zhang	Fontoura					
Person First Name	liang	Liang	Beatriz					
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Person Email	liang6.zhang@utsouthwestern.edu							
Person Affiliation	utsw							
Person Phone	2146483658							
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Person Address	utsw, 5323 harry hines blvd k2.202, Dallas, Texas, USA							
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Protocol Name	P-GSE35113-1	P-GSE35113-6	P-GSE35113-3	P-GSE35113-8	P-GSE35113-7	P-GSE35113-2	P-GSE35113-4	P-GSE35113-5
Protocol Description	ID_REF = <br>VALUE = quantile normalized	Standard Illumina hybridization protocol	293T cells were plated in 10 cm diameter dishes in DMEM containing 10% fetal calf serum.	The data were normalised using quantile normalisation with IlluminaGUI in R	Standard Illumina scanning protocol	Reagents were added at the concentrations and for the times listed on each sample.	For each sample total/cytoplasmic/nuclear RNA was isolated with Trizol and RNA was delivered to the UT Southwestern Microarray Core Facility.	Biotinylated cRNA were prepared according  to UT Southwestern Microarray protocol for Illumina arrays
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Protocol Type	bioassay_data_transformation	hybridization	grow	feature_extraction	image_aquisition	specified_biomaterial_action	nucleic_acid_extraction	labeling
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Comment[SecondaryAccession]	GSE35113							
Comment[GEOLastUpdateDate]	2012-01-17
Comment[AEExperimentType]	transcription profiling by array							
Comment[GEOReleaseDate]	2012-01-17
Comment[ArrayExpressSubmissionDate]	2012-01-15
SDRF File	E-GEOD-35113.sdrf.txt