Disruption of nonsense-mediated decay by the multifunctional long-distance movement protein of Pea enation mosaic virus 2
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ABSTRACT:
ORGANISM(S): Nicotiana benthamiana
PROVIDER: GSE137256 | GEO | 2020/03/01
REPOSITORIES: GEO
Similar Datasets
Project description:RNA interference (RNAi) is a natural cellular mechanism to silence gene expression and is predominantly mediated by microRNAs (miRNAs) that target messenger RNA. Viruses can manipulate the cellular processes necessary for their replication by targeting the host RNAi machinery. This study explores the effect of human T-cell leukemia virus type 1 (HTLV-1) transactivating protein Tax on the RNAi pathway in the context of a chromosomally integrated viral long terminal repeat (LTR) using a CD4(+) T-cell line, Jurkat.
2012-08-09 | GSE39986 | GEO
Project description:Nonsense-mediated mRNA decay (NMD) is a eukaryotic RNA degradation pathway that targets for degradation faulty mRNAs with premature termination codons as well as many physiological mRNAs encoding full-length proteins. Consequently, NMD functions in both, quality control and post-transcriptional regulation of gene expression, and it has been implicated in the modulation of cancer progression. To investigate the role of NMD in cancer, we knocked out SMG7 in the HT1080 human fibrosarcoma cell line. SMG7 is involved in deadenylation-coupled exonucleolytic mRNA decay, one of the two main degradation pathways in mammalian NMD. Genome-wide proteomic and transcriptomic analyses confirmed that NMD is severely compromised in these SMG7-knockout HT1080 cells. We compared the oncogenic properties between the parental, the SMG7-knockout, and a rescue cell line in which we re-introduced both isoforms of SMG7. In parallel, we tested the effect of a drug inhibiting the NMD factor SMG1 on the HT1080 cells to distinguish NMD-dependent effects from putative NMD-independent functions of SMG7. Using cell-based assays as well as a mouse xenograft tumor model, we show that the oncogenic properties of the parental HT1080 cells areseverely compromised when NMD is inhibited. Molecular pathway analysis revealed a strong reduction of the matrix metalloprotease 9 (MMP9) gene expression in NMD-suppressed cells. Since MMP9 expression promotes cancer cell migration and invasion, metastasis and angiogenesis, its downregulation in NMD-suppressed cells explains, at least partially, their reduced tumorigenicity. Collectively, our findings emphasize the therapeutic potential of NMD inhibition for the treatment ofcertain types of cancer.
2023-09-19 | PXD041853 | Pride
Project description:Nonsense-mediated mRNA decay (NMD) is a eukaryotic RNA degradation pathway that targets for degradation faulty mRNAs with premature termination codons as well as many physiological mRNAs encoding full-length proteins. Consequently, NMD functions in both, quality control and post-transcriptional regulation of gene expression, and it has been implicated in the modulation of cancer progression. To investigate the role of NMD in cancer, we knocked out SMG7 in the HT1080 human fibrosarcoma cell line. SMG7 is involved in deadenylation-coupled exonucleolytic mRNA decay, one of the two main degradation pathways in mammalian NMD. Genome-wide proteomic and transcriptomic analyses confirmed that NMD is severely compromised in these SMG7-knockout HT1080 cells. We compared the oncogenic properties between the parental, the SMG7-knockout, and a rescue cell line in which we re-introduced both isoforms of SMG7. In parallel, we tested the effect of a drug inhibiting the NMD factor SMG1 on the HT1080 cells to distinguish NMD-dependent effects from putative NMD-independent functions of SMG7. Using cell-based assays as well as a mouse xenograft tumor model, we show that the oncogenic properties of the parental HT1080 cells are severely compromised when NMD is inhibited. Molecular pathway analysis revealed a strong reduction of the matrix metalloprotease 9 (MMP9) gene expression in NMD-suppressed cells. Since MMP9 expression promotes cancer cell migration and invasion, metastasis and angiogenesis, its downregulation in NMD-suppressed cells explains, at least partially, their reduced tumorigenicity. Collectively, our findings emphasize the therapeutic potential of NMD inhibition for the treatment of certain types of cancer.
2023-09-06 | GSE232333 | GEO
Project description:Nonsense-mediated mRNA decay (NMD) is a eukaryotic RNA degradation pathway that targets for degradation faulty mRNAs with premature termination codons as well as many physiological mRNAs encoding full-length proteins. Consequently, NMD functions in both, quality control and post-transcriptional regulation of gene expression, and it has been implicated in the modulation of cancer progression. To investigate the role of NMD in cancer, we knocked out SMG7 in the HT1080 human fibrosarcoma cell line. SMG7 is involved in deadenylation-coupled exonucleolytic mRNA decay, one of the two main degradation pathways in mammalian NMD. Genome-wide proteomic and transcriptomic analyses confirmed that NMD is severely compromised in these SMG7-knockout HT1080 cells. We compared the oncogenic properties between the parental, the SMG7-knockout, and a rescue cell line in which we re-introduced both isoforms of SMG7. In parallel, we tested the effect of a drug inhibiting the NMD factor SMG1 on the HT1080 cells to distinguish NMD-dependent effects from putative NMD-independent functions of SMG7. Using cell-based assays as well as a mouse xenograft tumor model, we show that the oncogenic properties of the parental HT1080 cells are severely compromised when NMD is inhibited. Molecular pathway analysis revealed a strong reduction of the matrix metalloprotease 9 (MMP9) gene expression in NMD-suppressed cells. Since MMP9 expression promotes cancer cell migration and invasion, metastasis and angiogenesis, its downregulation in NMD-suppressed cells explains, at least partially, their reduced tumorigenicity. Collectively, our findings emphasize the therapeutic potential of NMD inhibition for the treatment of certain types of cancer.
2023-09-04 | GSE232185 | GEO
Project description:West Nile virus (WNV) is an emerging mosquito-borne flavivirus, related to dengue virus and Zika virus. To gain insight into host pathways involved in WNV infection, we performed a systematic affinity-tag purification mass spectrometry (AP-MS) study to identify 259 WNV-interacting human proteins. RNAi screening revealed 26 genes that both interact with WNV proteins and influence WNV infection. We found that WNV, dengue and Zika virus capsids interact with a conserved subset of proteins that impact infection. These include the exon-junction complex (EJC) recycling factor, PYM1, which is antiviral against all three viruses. The EJC has roles in nonsense-mediated decay (NMD), and we found that both the EJC and NMD are antiviral. Mechanistically, we found that the EJC protein RBM8A directly binds WNV RNA. To counteract this antiviral defense, flavivirus infection inhibits NMD and the interaction of capsid with PYM1 interferes with EJC protein function and localization. Moreover, depletion of PYM1 attenuates RBM8A binding to viral RNA, suggesting that WNV sequesters PYM1 to protect viral RNA from decay. Together, these data suggest a complex interplay between the virus and host in regulating NMD and the EJC complex.
2019-11-14 | PXD011728 | Pride
Project description:Aphids are sap-feeding insects with piercing-sucking mouthparts. They are serious pests in agriculture and provoke significant losses, with a formidable capacity to transmit numerous plant viruses causing diseases in almost all important crops. The majority of viruses are acquired after feeding on an infected plant, retained on the aphid’s stylet and inoculated to healthy ones with a single probing puncture, promoting viral outbreaks. We have recently discovered the acrostyle, an organ located at the tip of aphid maxillary stylets, that harbors the receptors for Cauliflower Mosaic Virus (CaMV), and likely those for numerous other viruses. To our opinion, establishing an exhaustive inventory of the cuticular proteins composing the acrostyle, defining the peptide motifs accessible at the surface, identifying virus receptors among these proteins, will contribute to better understand virus/vector and plant/insect interactions at different scales including the molecular level. In this manuscript, we identify proteins or peptides at the surface of aphid stylets that might play a key role in plant virus binding. This may help to pave the way for future alternative “environmentally safe” strategies to control viral spread and aphid infestation in important crops worldwide.
2020-01-29 | PXD016517 | Pride
Project description:RNA interference (RNAi) is a natural cellular mechanism to silence gene expression and is predominantly mediated by microRNAs (miRNAs) that target messenger RNA. Viruses can manipulate the cellular processes necessary for their replication by targeting the host RNAi machinery. This study explores the effect of human T-cell leukemia virus type 1 (HTLV-1) transactivating protein Tax on the RNAi pathway in the context of a chromosomally integrated viral long terminal repeat (LTR) using a CD4(+) T-cell line, Jurkat. Jurkat cells with stably integrated HTLV1-LTR were transfected with either pCMV-Tax or pCMV. Total miRNA was isolated, labeled and hybridized to the miRNA microarray as described by the manufacturer (Invitrogen). The hybridized slides were then analyzed on a GenePix scanner.
2012-08-08 | E-GEOD-39986 | biostudies-arrayexpress
Project description:Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe clinical symptoms and mortality in humans. Haemaphysalis longicornis tick has been identified as the competent vector for SFTSV transmission. Although antiviral RNA interference (RNAi) in insects has been well documented, the degree to which RNAi contributes to antiviral defense in ticks is still largely elusive. In this study, utilizing arthropod-borne RNA viruses, including SFTSV, we find abundant virus-derived small interfering RNAs (vsiRNAs) are induced in H. longicornis after infection through either microinjection or natural blood-feeding. Furthermore, we identify a Dicer2-like homolog, the core protein of antiviral RNAi pathway, in H. longicornis and knocking down this gene exacerbated virus amplification. To counteract this antiviral RNAi of ticks, viruses have evolved suppressors of RNAi (VSRs). Here, we show that reduced viral replication inversely correlated with the accumulation of vsiRNAs in ticks after infection with recombinant sindbis virus (SINV) expressing heterologous VSR proteins. Elucidating the antiviral RNAi pathway of ticks by model arthropod-borne RNA viruses in vivo is critical to understanding the virus-host interaction, providing a feasible intervention strategy to control tick-borne arbovirus transmission.
2024-01-16 | GSE165139 | GEO
Project description:RNA quality control pathways serve to get rid of faulty RNAs and therefore must be able to discriminate these RNAs from those that are normal. Here we present evidence that the ATPase cycle of SF1 Helicase Upf1 is required for mRNA discrimination during Nonsense-Mediated Decay (NMD). Mutations affecting the Upf1 ATPase cycle disrupt the mRNA selectivity of Upf1, leading to indiscriminate accumulation of NMD complexes on both NMD target and non-target mRNAs. In addition, two modulators of NMD - translation and termination codon-proximal poly(A) binding protein - depend on Upf1 ATPase to limit Upf1-non-target association. Preferential ATPase-dependent dissociation of Upf1 from non-target mRNAs in vitro suggests that selective release of Upf1 contributes to the ATPase-dependence of Upf1 target discrimination. Given the prevalence of helicases in RNA regulation, ATP hydrolysis may be an underappreciated, yet widely employed, activity in target RNA discrimination. CLIP and RIP-seq against Wild Type and Mutant Upf1 in HEK293-T cell lines
2015-07-06 | E-GEOD-69584 | biostudies-arrayexpress
Project description:RNA quality control pathways serve to get rid of faulty RNAs and therefore must be able to discriminate these RNAs from those that are normal. Here we present evidence that the ATPase cycle of SF1 Helicase Upf1 is required for mRNA discrimination during Nonsense-Mediated Decay (NMD). Mutations affecting the Upf1 ATPase cycle disrupt the mRNA selectivity of Upf1, leading to indiscriminate accumulation of NMD complexes on both NMD target and non-target mRNAs. In addition, two modulators of NMD - translation and termination codon-proximal poly(A) binding protein - depend on Upf1 ATPase to limit Upf1-non-target association. Preferential ATPase-dependent dissociation of Upf1 from non-target mRNAs in vitro suggests that selective release of Upf1 contributes to the ATPase-dependence of Upf1 target discrimination. Given the prevalence of helicases in RNA regulation, ATP hydrolysis may be an underappreciated, yet widely employed, activity in target RNA discrimination. CLIP and RIP-seq against Wild Type and Mutant Upf1 in HEK293-T cell lines
2015-07-06 | E-GEOD-69585 | biostudies-arrayexpress