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E-GEOD-35113 - Genome-wide analysis of gene expression and nuclear/cytoplasmic distribution by compound 1 treatment [293T_NS1-1]

Status
Released on 17 January 2012, last updated on 23 January 2012
Organism
Homo sapiens
Samples (6)
Array (1)
Protocols (8)
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
Experiment type
transcription profiling by array 
Contacts
liang zhang <liang6.zhang@utsouthwestern.edu>, Beatriz Fontoura, Liang Zhang
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-35113.idf.txt
Sample and data relationshipE-GEOD-35113.sdrf.txt
Processed data (1)E-GEOD-35113.processed.1.zip
Array designA-GEOD-13475.adf.txt
Links