Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1086021 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Purpose: SARS-CoV-2 is a betacoronavirus responsible for the COVID-19 pandemic. Currently, limited understanding of the molecular and structural biology of the virus hampers the development of antiviral drugs. Methods: Vero cells were infected with SARS-CoV-2 and treated with dimethyl sulfate (DMS). RNA was extracted, reverse-transcribed using TGIRT-III, PCR-amplified, and sequenced using an Illumina iSeq100. Reads were trimmed with TrimGalore and mapped to the SARS-CoV-2 genome with Bowtie2. Mutations were quantified with DREEM, and the frequencies were used as folding constraints in RNAstructure. The output structures were visualized with VARNA. Results: A data-driven secondary structure of the full RNA genome was generated, including structures previously lacking experimental validation, such as the TRSs. An alternative structure was identified for the frameshift element that differs drastically from previous in vitro models. The canonical frameshift element pseudoknot was not detected; in its place was an alternative stem partially overlapping with the canonical pseudoknot. Two alternative structures containing this stem were identified. Conclusions: The genome-wide structure of SARS-CoV-2 provides a basis for developing therapeutics targeted to key regulatory structures. In particular, the model suggests that frameshifting is caused by a novel 75 nt stem rather than the canonical pseudoknot, which will guide the search for therapeutics that disrupt frameshifting..
2020-09-01 | GSE153851 | GEO
Project description:Programmed ribosomal frameshifting (PRF) is a fundamental gene expression event in many viruses, including SARS-CoV-2. It allows production of essential viral structural and replicative enzymes that are encoded in an alternative reading frame. Despite the importance of PRF for the viral life cycle, it is still largely unknown how and to what extent cellular factors alter mechanical properties of frameshift elements and thereby impact virulence. This prompted us to comprehensively dissect the interplay between the SARS-CoV-2 frameshift element and the host proteome. We reveal that the short isoform of the zinc-finger antiviral protein (ZAP-S) is a direct regulator of PRF in SARS-CoV-2 infected cells. ZAP-S overexpression strongly impairs frameshifting and inhibits viral replication. Using in vitro ensemble and single-molecule techniques, we further demonstrate that ZAP-S directly interacts with the SARS-CoV-2 RNA and interferes with the folding of the frameshift RNA element. Together, these data identify ZAP-S as a host-encoded inhibitor of SARS-CoV-2 frameshifting and expand our understanding of RNA-based gene regulation.
2021-11-25 | PXD029656 | Pride
Project description:This dataset looks at the transcriptome of in vitro-differentiated primary lung cells infected with SARS-CoV2. Some cells have been treated with the drug Enzalutamide.
2022-05-04 | E-MTAB-10687 | biostudies-arrayexpress
Project description:RNA-Seq was carried out in order to obtain the time dependent expression dynamics of SARS-CoV2 (Trondheim strain)-induced transcriptome changes in human lung epithelial Calu-3 cells.
2022-10-25 | E-MTAB-12134 | biostudies-arrayexpress
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus diseases 2019 (COVID-19) and broncho-alveolar inflammation (Merad and Martin, 2020). IL-9 induces airway inflammation and bronchial hyper responsiveness in respiratory viral illnesses and allergic inflammation (Temann et al., 1998). However, the role of IL-9 is not yet identified in SARS-CoV2 infection. Here we show that IL-9 promotes SARS-CoV2 infection and airway inflammation in K18-hACE2 transgenic (ACE2.Tg) mice, as IL-9 blockade reduces SARS-CoV2 infection and suppressed airway inflammation. Foxo1 is essential for the induction of IL-9 in helper T (Th) cells (Malik et al., 2017). While ACE2.Tg mice with Foxo1-deficiency in CD4+ T cells were performed to be resistant to SARS-CoV2 infection associated with reduced IL-9 production, exogenous IL-9 made Foxo1-deficient mice susceptible to SARS-CoV2 infection with increased airway inflammation. Collectively, we identify a mechanistic insight of IL-9-mediated regulation of antiviral and inflammatory pathways in SARS-CoV2 infection, and unravel a principle for the development of host-directed therapeutics to mitigate disease severity.
2022-07-22 | GSE209550 | GEO
Project description:RNAseq analysis of human immune cells (monocytes CD14+ and B cells CD19+) cocultured with SARS-CoV2, influenza A or Ebola viruses-infected epithelial cells as well as directly infected or SARS-CoV2 single protein transfected epithelial cells
2021-10-29 | GSE186650 | GEO
Project description:The SARS-CoV-2 coronavirus, which causes the COVID-19 pandemic, is one of the largest positive strand RNA viruses. Here we developed a simplified SPLASH assay and comprehensively mapped the in vivo RNA-RNA interactome of SARS-CoV-2 RNA during the viral life cycle. We observed canonical and alternative structures including 3’-UTR and 5’-UTR, frameshifting element (FSE) pseudoknot and genome cyclization in cells and in virions. We provide the first evidence of comprehensive interactions between Transcription Regulating Sequences (TRS-L and TRS-Bs), which facilitate discontinuous transcription. In addition, we find alternative short and long distance arches around FSE, forming a “high-order pseudoknot” embedding FSE, which might help ribosome stalling at frameshift sites. We found that during packaging, SARS-CoV-2 genome RNA undergoes compaction while genome domains remain stable and genome cyclization is weakened. Our data provides a structural basis for the regulation of replication, discontinuous transcription and translational frameshifting describes dynamics on RNA structures during life cycle of SARS-CoV-2, and will help to develop antiviral strategies.
2021-08-29 | GSE164565 | GEO
Project description:Programmed ribosomal frameshifting is the key event during translation of the SARS-CoV-2 RNA genome allowing synthesis of the viral RNA-dependent RNA polymerase and downstream viral proteins. Here we present the cryo-EM structure of the mammalian ribosome in the process of translating viral RNA paused in a conformation primed for frameshifting. We observe that the viral RNA adopts a pseudoknot structure lodged at the mRNA entry channel of the ribosome to generate tension in the mRNA that leads to frameshifting. The nascent viral polyprotein that is being synthesized by the ribosome paused at the frameshifting site forms distinct interactions with the ribosomal polypeptide exit tunnel. We use biochemical experiments to validate our structural observations and to reveal mechanistic and regulatory features that influence the frameshifting efficiency. Finally, a compound previously shown to reduce frameshifting is able to inhibit SARS-CoV-2 replication in infected cells, establishing coronavirus frameshifting as target for antiviral intervention.
2021-05-17 | GSE167421 | GEO
Project description:This study addresses the question how host cells transcriptionally respond to SARS-CoV2 infection.
2023-12-02 | GSE162492 | GEO