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Polysome purified mRNA in control and RACK1 silenced in human hepatocarcinoma cells

ABSTRACT: Fighting viral infections is hampered by the scarcity of viral targets and their variability resulting in development of resistance. Viruses depend on cellular molecules for their life cycle, which are attractive alternative targets, provided that they are dispensable for normal cell functions. Using the model organism Drosophila melanogaster, we identify the ribosomal protein RACK1 as a cellular factor required for infection by internal ribosome entry site (IRES)-containing viruses. We further show that RACK1 is an essential determinant for hepatitis C virus translation and infection indicating that its function is conserved among distantly related human and fly viruses. Inhibition of RACK1 does not affect Drosophila or human cell viability and proliferation, and RACK1-silenced adult flies are viable, indicating that this protein is not essential for general translation. Our findings demonstrate a specific function for RACK1 in selective mRNA translation and uncover a new target for the development of broad antiviral intervention.

ORGANISM(S): Homo sapiens

PROVIDER: GSE60374 | GEO | 2015/05/14

SECONDARY ACCESSION(S): PRJNA258133

REPOSITORIES: GEO

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Polysome purified mRNA in control and RACK1 silenced in human hepatocarcinoma cells

Project description:Fighting viral infections is hampered by the scarcity of viral targets and their variability resulting in development of resistance. Viruses depend on cellular molecules for their life cycle, which are attractive alternative targets, provided that they are dispensable for normal cell functions. Using the model organism Drosophila melanogaster, we identify the ribosomal protein RACK1 as a cellular factor required for infection by internal ribosome entry site (IRES)-containing viruses. We further show that RACK1 is an essential determinant for hepatitis C virus translation and infection indicating that its function is conserved among distantly related human and fly viruses. Inhibition of RACK1 does not affect Drosophila or human cell viability and proliferation, and RACK1-silenced adult flies are viable, indicating that this protein is not essential for general translation. Our findings demonstrate a specific function for RACK1 in selective mRNA translation and uncover a new target for the development of broad antiviral intervention. 4 Controls 4 RACK1 silenced cells

2015-05-14 | E-GEOD-60374 | biostudies-arrayexpress

RACK1 associates with RNA-binding proteins Vigilin and SERBP1 to influence dengue virus replication

Project description:Dengue virus (DENV), a re-emerging virus transmitted by Aedes mosquitoes, causes severe pathogenesis in humans. No effective treatment is available against this virus. We recently identified the scaffold protein RACK1 as a component of the DENV replication complex, a macromolecular complex essential for viral genome amplification. Here, we show that RACK1 is important for DENV infection. RACK1 mediates DENV replication through binding to the 40S ribosomal subunit. Mass spectrometry analysis of RACK1 partners coupled to a loss-of-function screen identified the RNA binding proteins Vigilin and SERBP1 as DENV host dependency factors. Vigilin and SERBP1 interact with DENV viral RNA (vRNA), forming a ternary complex with RACK1 to mediate viral replication. Overall, our results indicate that RACK1 recruits Vigilin and SERBP1, linking the DENV vRNA to the translation machinery for optimal translation and replication.

2022-02-04 | PXD030765 | Pride

The cytokine DIEDEL and a viral homologue suppress deleterious IMD-dependent gene expression in drosophila

Project description:Viral infection in Drosophila triggers inducible gene expression, but the function of many of these genes and the biological significance of their induction remain poorly understood. Here, we report the functional characterization of the gene Diedel, which is strongly induced following some viral infections and encodes a 12kDa circulating protein. Diedel mutant flies have reduced viability and succumb rapidly to infection with Sindbis virus. This phenotype is associated with deregulated expression of IMD target genes and is rescued by mutations in the genes imd or IKKg, indicating that Diedel functions as an immunosuppressor cytokine targeting the IMD pathway. Homologues of Diedel are found in the genome of several DNA viruses, providing the first example of virokines in insects. Our results reveal that, besides RNA interference and apoptosis, an NF-kB pathway of inducible defense exerts evolutionary pressure on insect viruses. For each experimental condition (non infected and SINV infected), two biologically independent samples composed of 45 males of w1118 or Diedelcfm null mutant flies were used. Infection has been performed by injecting viral stocks prepared in Tris solution. Flies were then incubated for days at 29Â°C.

2016-01-07 | E-GEOD-68174 | biostudies-arrayexpress

High throughput sequencing of small RNAs from Drosophila cells infected with a panel of viruses

Project description:We report the cloning and sequencing of both endogenous small RNAs and virus-derived siRNAs produced by the antiviral RNAi pathway in Drosophila. We find that a diverse panel of viruses are targeted by the RNAi pathway in Drosophila to produce abundant virus-derived siRNAs, and these siRNAs map to various locations within the viral genomes. Knockdown of various RNAi and miRNA pathway components alters the levels of these viral small RNAs. Drosophila DL1 cells were treated with dsRNA for 3 days to deplete factors involved in the antiviral RNAi pathway and miRNA pathway, then were challenged with one of four viruses for 4 days. Total RNA was collected, and the small RNA populations from 15-29 nt were cloned and sequenced.

2013-01-01 | E-GEOD-43031 | biostudies-arrayexpress

The cytokine DIEDEL and a viral homologue suppress deleterious IMD-dependent gene expression in drosophila

2016-01-07 | GSE68174 | GEO

Virus-induced codon-specific reprogramming to favor viral RNA translation

Project description:How viruses, such as the emerging mosquito-borne Chikungunya virus (CHIKV), express their genomes at high levels despite an enrichment in suboptimal codons remains a puzzling question. By integrating subcellular fractionation and transcriptome-wide analyses of translation in CHIKV-infected human cells, we demonstrate an unanticipated virus-induced reprogramming of the host translation machinery to favor translation of viral RNA over cellular genes featuring optimal codon usage. This reprogramming was specifically apparent at the endoplasmic reticulum (ER), the preferred translation compartment of CHIKV RNA, and it is mediated by the wobble uridine 34 tRNA modification enzyme KIAA1456 whose expression is enhanced upon viral infection. Since KIAA1456 itself is encoded by a CHIKV-like codon usage, infection triggers a positive feed-back loop that ensures efficient virus protein production. Our findings demonstrate an unprecedented interplay of viruses with the host tRNA epitranscriptome to favor viral protein expression.

2022-06-17 | GSE143390 | GEO

RNA-Seq of U2OS cells with and without IFNα2 pretreatment

Project description:RNA viruses are among the most prevalent pathogens and represent a major burden on society. While RNA viruses have been studied extensively, little is known about the processes that occur during the first several hours of infection due to a lack of sensitive assays. Here, we develop a single-molecule imaging assay, virus infection real-time imaging (VIRIM), to study translation and replication of individual RNA viruses in live cells. VIRIM uncovered a striking heterogeneity in replication dynamics between cells and revealed extensive coordination between translation and replication of single viral RNAs. Furthermore, using VIRIM we identify the replication step of the incoming viral RNA as a major bottleneck of successful infection, and identify host genes that are responsible for inhibition of early virus replication. Single-molecule imaging of virus infection represents a powerful tool to study virus replication and virus-host interactions that may be broadly applicable to RNA viruses.

2020-11-18 | GSE159280 | GEO

RACK1 interactome in drosophila S2 cells (FLAG-tag), using DDA and DIA (SWATH) approaches

Project description:Receptor for Activated C kinase 1 (RACK1) is a scaffold protein that has been found in association with several signaling complexes, and with the 40S subunit of the ribosome. Data presented here allowed a proteomic characterization of the interactome of RACK1 in drosophila S2 cells. We carried out Label-Free quantitation using both Data-Dependent (DDA) and Data-Independent Acquisition (DIA, SWATH). This study is a 2-factor experiment, where control samples (RACK1 overexpressed with a HA tag) were compared to IP samples (RACK1 overexpressed with a FLAG tag), in either mock or infected cells. Each of these 6 conditions were performed in biological triplicates.

2017-05-29 | PXD002965 | Pride

The ribosomal protein Asc1/RACK1 is required for efficient translation of short mRNAs

Project description:Translation is a core cellular process carried out by a highly conserved macromolecular machine, the ribosome. There has been remarkable evolutionary adaptation of this machine through the addition of eukaryote-specific ribosomal proteins whose individual effects on ribosome function are largely unknown. Here we show that eukaryote-specific Asc1/RACK1 is required for efficient translation of mRNAs with short open reading frames that show greater than average translational efficiency in diverse eukaryotes. ASC1 mutants in S. cerevisiae display compromised translation of specific functional groups, including cytoplasmic and mitochondrial ribosomal proteins, and display cellular phenotypes consistent with their gene-specific translation defects. Asc1-sensitive mRNAs are preferentially associated with the translational ‘closed loop’ complex comprised of eIF4E, eIF4G and Pab1, and depletion of eIF4G mimics the translational defects of ASC1 mutants. Together our results reveal a role for Asc1/RACK1 in a length-dependent initiation mechanism optimized for efficient translation of genes with important housekeeping functions.

2016-04-24 | GSE61753 | GEO

CAGE sequencing of LASV infected Vero Cells

Project description:We report a novel mechanism of gene origination in the segmented negative sense viruses (sNSVs), including IAV and LASV. During replication, these viruses use "snatched" host caps to prime their own transcription (cap-snatching). We show that a proportion of cap-snatched host sequences contain translational start codons (AUGs), that are recognized by the host ribosome. This allows for the translation of host and viral “untranslated regions” (UTRs) to create N-terminally extended viral proteins or entirely novel polypeptides by genetic overprinting.

2020-05-31 | GSE148122 | GEO

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