|
| Status |
Public on Jan 17, 2012 |
| Title |
Genome-wide analysis of gene expression and nuclear/cytoplasmic distribution by compound 1 treatment [293T_NS1-2] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
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| |
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| Overall design |
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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| |
|
| Contributor(s) |
Zhang L, Fontoura B |
| Citation(s) |
22312003 |
| Submission date |
Jan 15, 2012 |
| Last update date |
Aug 13, 2018 |
| Contact name |
liang zhang |
| E-mail(s) |
liang6.zhang@utsouthwestern.edu
|
| Phone |
2146483658
|
| Organization name |
utsw
|
| Lab |
zhang
|
| Street address |
5323 harry hines blvd k2.202
|
| City |
Dallas |
| State/province |
Texas |
| ZIP/Postal code |
75390 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
|
| Samples (12)
|
| GSM862250 |
cytoplasmic RNA after empty vector transfection (16h) and DMSO treatment(24h) |
| GSM862251 |
total RNA after empty vector transfection (16h) and DMSO treatment(24h) |
| GSM862252 |
cytoplasmic RNA after empty vector transfection (16h) and compound 1(5uM) treatment(24h) |
| GSM862253 |
total RNA after empty vector transfection (16h) and compound 1(5uM) treatment(24h) |
| GSM862254 |
cytoplasmic RNA after NS1 transfection (16h) and DMSO treatment(24h) |
| GSM862255 |
total RNA after NS1 transfection (16h) and DMSO treatment(24h) |
| GSM862256 |
cytoplasmic RNA after NS1 transfection (16h) and compound 1(5uM) treatment(24h) |
| GSM862257 |
total RNA after NS1 transfection (16h) and compound 1(5uM) treatment(24h) |
| GSM862258 |
nuclear RNA after NS1 transfection (16h) and DMSO treatment(24h) |
| GSM862259 |
nuclear RNA after NS1 transfection (16h) and compound 1(5uM) treatment(24h) |
| GSM862260 |
nuclear RNA after empty vector transfection (16h) and DMSO treatment(24h) |
| GSM862261 |
nuclear RNA after empty vector transfection (16h) and compound 1(5uM) treatment(24h) |
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| This SubSeries is part of SuperSeries: |
| GSE35117 |
Analysis of cellular responsive nuclear/cytoplasmic mRNA distribution to viral virulence factor and dihydroorotate dehydrogenase (DHODH) inhibition |
|
| Relations |
| BioProject |
PRJNA156009 |
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