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The translational landscape of HIV-1 1 infected cells reveals novel gene regulatory principles

ABSTRACT: The translational landscape of HIV-1 1 infected cells reveals novel gene regulatory principles

PROVIDER: PRJNA1023231 | ENA |

REPOSITORIES: ENA

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The translational landscape of HIV-1 1 infected cells reveals novel gene regulatory principles

Project description:Human Immunodeficiency Virus-1 (HIV-1) uses a number of strategies to modulate viral and host gene expression during its lifecycle. To characterize the transcriptional and translational landscape of HIV-1 infected cells, we used a combination of ribosome profiling, disome sequencing and RNA sequencing. We show that HIV-1 mRNAs are efficiently translated at all stages of infection, despite evidence for a substantial decrease in translational efficiency of host genes that are implicated in host cell translation. Our data also reveal novel upstream open reading frames (uORFs) within the HIV-1 5' UTR as well as internal ORFs (iORFs) within the Vif and Pol coding domains. We observed ribosomal collisions in Gag-Pol upstream of the ribosome frameshift site that we attributed to a novel RNA structural fold using RNA structural probing and functional analysis. Antisense oligos designed to alter the base of this structure decreased frameshift efficiency. Overall, our data highlights the complexity of HIV-1 gene regulation and provides a key resource for decoding of host-pathogen interactions upon HIV-1 infection. Furthermore, we provide evidence for a novel RNA structural fold including the frameshift site that might be promising as a target for antiviral therapy.

2024-11-26 | GSE244468 | GEO

Higher-Order Organization Principles of Pre-translational mRNPs [RIPPLiT]

Project description:Higher-Order Organization Principles of Pre-translational mRNPs [RIPPLiT]

| PRJNA476057 | ENA

Translational landscape of SARS-CoV-2 and infected cells

Project description:Translational landscape of SARS-CoV-2 and infected cells

| PRJNA667051 | ENA

Translational landscape of SARS-CoV-2 and infected cells

Project description:Purpose: Numerous viruses manipulate the host translation machinery and specifically block host mRNA translation. The goal of this study is to define the translational landscape of SARS-CoV-2 and SARS-CoV-2 infected cells using a combination of RNA-seq and ribo-seq approches, the latter being a powerful proxy for protein-level changes. Methods: Vero E6 and primary human bronchial epithelial cells were infected with SARS-CoV-2 at varying multiplicities of infection and followed throughout early and late phases of infection. Parallel samples were processed for RNA-seq and Ribo-seq. Sequencing reads were cleaned off of adapters and rRNAs. Reads were first mapped to the SARS-CoV-2 genome and then to the African green monkey and human genomes using STAR. Mapped reads were further annotated and processed using publicly available software and custom scripts deposited at Github. DE gene expression analysis was performed usign EdgeR. Gene set enrichment analysis was done using TcGSA. Results: We provide the transcriptomic and translatomic landscape of SARS-CoV-2-infected cells from multiple RNA-seq and ribo-seq libraries. We found that the robust transcriptional upregulation of numerous chemokines and cytokines are translationally blocked in SARS-CoV-2-infected cells. Conclusions: Our study represents the first detailed analysis of viral and host translational landscape in infected cells and demonstrate that translation of host mRNAs involved in innate immunity is specifically blocked. The optimized data analysis workflows reported here should provide a framework for translational profiling studies in other settings.

2020-11-23 | GSE158930 | GEO

Characterization of the epitranscriptomic landscape of HIV-infected cells

Project description:Characterization of the epitranscriptomic landscape of HIV-infected cells

| PRJNA660413 | ENA

Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway remodeling

Project description:Viruses must effectively remodel host cellular pathways to replicate and evade immune defenses, and they must do so with limited genomic coding capacity. Targeting post-translational modification (PTM) pathways provides a mechanism by which viruses can broadly and rapidly transform a hostile host environment into a hospitable one. We used mass spectrometry-based proteomics to quantify changes in protein abundance and two PTM types – phosphorylation and ubiquitination – in response to HIV-1 infection with viruses harboring targeted deletions of a subset of HIV-1 genes. PTM analysis revealed a requirement for Aurora kinase activity in HIV-1 infection and identified substrates of a phosphatase that is degraded during infection. Finally, we demonstrated that the Cullin4A-DDB1-DCAF1 E3 ubiquitin ligase ubiquitinates histone H1 somatic isoforms and that the HIV-1 Vpr protein inhibits this process, leading to defects in DNA repair.

2022-04-14 | PXD032085 | Pride

The translational landscape of ground state pluripotency

Project description:The translational landscape of ground state pluripotency

| PRJNA552550 | ENA

Characterization of the epitranscriptomic landscape of HIV-infected cells I

Project description:Characterization of the epitranscriptomic landscape of HIV-infected cells I

| PRJNA660416 | ENA

Characterization of the epitranscriptomic landscape of HIV-infected cells II

Project description:Characterization of the epitranscriptomic landscape of HIV-infected cells II

| PRJNA660417 | ENA

Characterization of the epitranscriptomic landscape of HIV-infected cells III

Project description:Characterization of the epitranscriptomic landscape of HIV-infected cells III