 |
 |
GEO help: Mouse over screen elements for information. |
|
Status |
Public on Aug 09, 2016 |
Title |
Genome-wide analysis of Dengue virus 2 infected cells |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
The goal of this study was to compare the transcriptional profile (RNA-seq) of Dengue virus 2 and mock infected cells at 24 and 36 hours post infection. Dengue virus NS5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral RNA replication and counteracting host antiviral responses. Here, we demonstrate a novel function of NS5 in the nucleus where it interferes with cellular splicing. Using global proteomic analysis of infected cells together with functional studies, we found that NS5 binds spliceosome complexes and modulates endogenous splicing. In particular, we show that NS5 alone, or in the context of viral infection, interacts with core components of the U5 snRNP particle, CD2BP2 and DDX23, alters the inclusion/exclusion ratio of alternative splicing events, and changes mRNA isoform abundance of known antiviral factors. Interestingly, a genome wide transcriptome analysis, using recently developed bioinformatics tools, revealed an increase of intron retention upon dengue virus infection, and viral replication was improved by silencing specific U5 components. Different mechanistic studies indicate that binding of NS5 to the spliceosome reduces the efficiency of pre-mRNA processing, independently of NS5 enzymatic activities. We propose that NS5 binding to U5 snRNP proteins hijacks the splicing machinery resulting in a less restrictive environment for viral replication.
|
|
|
Overall design |
A549 cells where infected with Dengue virus 2 or mock and after 24 and 36 hours post infection mRNA was purified. Then the transcriptional profile of these cells was analyzed using RNA-seq.
|
|
|
Contributor(s) |
De Maio F, Risso G, Iglesias G, Shah P, Pozzi B, Gebhard L, Mammi P, Mancini E, Yanovsky M, Andino R, Krogan N, Srebrow A, Gamarnik A |
Citation(s) |
27575636 |
|
Submission date |
Jul 12, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Andrea Gamarnik |
E-mail(s) |
agamarnik@leloir.org.ar
|
Organization name |
Fundacion Instituto Leloir
|
Street address |
Av. Patricias Argentinas 435
|
City |
Ciudad Autonoma de Buenos Aires |
ZIP/Postal code |
C1405BWE |
Country |
Argentina |
|
|
Platforms (1) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
Samples (12)
|
|
Relations |
BioProject |
PRJNA328591 |
SRA |
SRP078309 |
Supplementary file |
Size |
Download |
File type/resource |
GSE84285_bin_counts_24h.xlsx |
29.4 Mb |
(ftp)(http) |
XLSX |
GSE84285_bin_counts_36h.xlsx |
29.3 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
|
|
|
|
 |