Viral-mediated ubiquitination impacts interactions of host proteins with viral RNA and promotes viral RNA processing
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA607121 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11097360.fastq.gz | Fastqsanger.gz | |||
| SRR11097361.fastq.gz | Fastqsanger.gz | |||
| SRR11097362.fastq.gz | Fastqsanger.gz | |||
| SRR11097363.fastq.gz | Fastqsanger.gz | |||
| SRR11097364.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 9 |
Similar Datasets
Project description:Viruses promote infection by hijacking the host ubiquitin machinery to counteract or redirect cellular processes. Adenovirus encodes two early proteins, E1B55K and E4orf6, that together co-opt a cellular ubiquitin ligase complex to overcome host defenses and promote virus production. Adenovirus mutants lacking E1B55K or E4orf6 display defects in viral RNA processing and protein production, but previously identified substrates of the ligase do not explain these phenotypes. Here we used a quantitative proteomics approach to identify substrates of E1B55K/E4orf6 that are ubiquitinated to facilitate RNA processing. While cellular proteins known as substrates of E1B55K/E4orf6 are degraded by the proteasome, we uncovered RNA-binding proteins (RBPs) as high-confidence substrates which are not decreased in overall abundance. We focused on two predominant RBPs, RALY and hnRNP-C, which we confirm are ubiquitinated without degradation. Knockdown of RALY and hnRNP-C rescued levels of viral RNA splicing, protein, and progeny production during infection with E1B55K-deleted virus. Furthermore, deletion of E1B55K resulted in increased interaction of hnRNP-C with viral RNA and attenuation of viral RNA processing. These data suggest viral-mediated ubiquitination of RALY and hnRNP-C relieves a restriction on viral RNA processing, revealing an unexpected role for non-degradative ubiquitination in the manipulation of cellular processes during virus infection.
2020-07-09 | GSE145411 | GEO
Project description:Hepatitis E virus (HEV) is a globally prevalent pathogen that causes 20 million infections and 60,000 fatalities annually, endangering particularly pregnant women and immunosuppressed individuals. Liver cirrhosis, which results from advanced fibrosis, is the primary symptom and leading mortality cause in chronic hepatitis E patients. However, the causation and process of liver fibrosis triggered by chronic HEV infection remain poorly understood. Here, we unexpectedly discovered that the viral multiple-domain replicase (ORF1) undergoes unique ubiquitin-proteasomal processing in HEV replicon hepatocytes, HEV-infected gerbil livers, and HEV-infected patient livers, which follows a CHIP-mediated K48 ubiquitination and produces the HEV-Derived Smad Activator (HDSA). Lacking putative helicase and RNA polymerase domains, this enriched viral polypeptide in hepatocytes and gerbil livers is non-HSP90-bound, stable, and exhibits exclusively nuclear localization. Surprisingly, HDSA markedly potentiates the fibrogenic TGF-β/Smad pathway in livers by facilitating promoter binding and coactivator recruitment of SMAD3, leading to profound liver fibrotic symptoms and damage. Thus, we have identified the first viral protein derived from the unique proteasomal processing of the host, defined its notable role in liver fibrosis, and highlighted the nature of complex host-HEV interactions that drives HEV pathogenesis.
2024-08-01 | GSE251924 | GEO
Project description:HIV-1 latency results from a combination of tightly regulated molecular processes that act at distinct steps of HIV-1 gene expression. In an effort to elucidate the molecular players that govern viral latency, we previously performed a dCas9 chromatin immunoprecipitation coupled with mass spectrometry (Catchet-MS) and identified proteins bound differentially to the latent LTR that putatively promote HIV-1 latency. Here we characterize the Catchet-MS identified PCI domain-containing 2 (PCID2) protein to play a dual role in promoting HIV-1 latency by enforcing both HIV-1 transcription repression as well as post-transcriptional blocks. PCID2 bound the latent HIV-1 LTR and repressed transcription initiation during latency. Depletion of PCID2 remodeled the chromatin landscape at the HIV-1 promoter and resulted in transcriptional activation and reversal of latency. Immunoprecipitation coupled to Mass Spectrometry identified the PCID2 interacting proteins to include members of the spliceosome and other splicing regulators, including negative regulators of viral RNA alternative splicing. PCID2 depletion resulted in over-splicing of intron-containing HIV-1 RNA and mis-regulated expression of vRNA splice variants. Finally, consistent with its role in NXF1-mediated nascent RNA nucleocytoplasmic export as part of the TREX2 complex, PCID2 modulates export of completely spliced vRNA. In summary, we demonstrate that PCID2 is a previously unidentified factor involved in HIV-1 latency regulation which plays a dual role in blocking HIV-1 gene expression by acting on transcription initiation as well as viral RNA processing.
2024-06-16 | PXD043334 | Pride
Project description:Viruses promote infection by hijacking the ubiquitin machinery of the host to counteract or redirect cellular processes. Adenovirus encodes two early proteins, E1B55K and E4orf6, that together co-opt a cellular ubiquitin ligase complex to overcome host defences and promote virus production. Adenovirus mutants lacking E1B55K or E4orf6 display defects in viral RNA processing and protein production, but previously identified substrates of the redirected ligase do not explain these phenotypes. Here, we used a quantitative proteomics approach to identify substrates of E1B55K/E4orf6-mediated ubiquitination that facilitate RNA processing. While all currently known cellular substrates of E1B55K and E4orf6 are degraded by the proteasome, we uncovered RNA-binding proteins as high-confidence substrates that are not decreased in overall abundance. We focused on two RNA-binding proteins, RALY and hnRNP-C, which we confirm are ubiquitinated without degradation. Knockdown of RALY and hnRNP-C increased levels of viral RNA splicing, protein abundance and progeny production during infection with E1B55K-deleted virus. Furthermore, infection with E1B55K-deleted virus resulted in an increased interaction of hnRNP-C with viral RNA and attenuation of viral RNA processing. These data suggest that viral-mediated ubiquitination of RALY and hnRNP-C relieves a restriction on viral RNA processing and reveal an unexpected role for non-degradative ubiquitination in the manipulation of cellular processes during virus infection.
| S-EPMC7529849 | biostudies-literature
Project description:PCID2 dysregulates transcription and viral RNA processing to promote HIV-1 latency
| PRJNA1049312 | ENA
Project description:RNA silencing is a post-transcriptional gene-silencing mechanism mediated by microRNAs (miRNAs). However, the regulatory mechanism of RNA silencing during viral infection is unclear. TAR RNA-binding protein (TRBP) is an enhancer of RNA silencing that induces miRNA maturation by interacting with the ribonuclease Dicer. TRBP interacts with a virus sensor protein, laboratory of genetics and physiology 2 (LGP2), in the early stage of viral infection of human cells. Next, it induces apoptosis by inhibiting the maturation of miRNAs, thereby upregulating the expression of apoptosis regulatory genes. In this study, we show that TRBP undergoes a functional conversion in the late stage of viral infection. Viral infection resulted in the activation of caspases that proteolytically processed TRBP into two fragments. The N-terminal fragment did not interact with Dicer but interacted with type I interferon (IFN) signaling modulators, such as protein kinase R (PKR) and LGP2, and induced ER stress. The end results were irreversible apoptosis and suppression of IFN signaling. Our results demonstrate that the processing of TRBP enhances apoptosis, reducing IFN signaling during viral infection.
2024-04-19 | GSE234549 | GEO
Project description:RNA silencing is a post-transcriptional gene-silencing mechanism mediated by microRNAs (miRNAs). However, the regulatory mechanism of RNA silencing during viral infection is unclear. TAR RNA-binding protein (TRBP) is an enhancer of RNA silencing that induces miRNA maturation by interacting with the ribonuclease Dicer. TRBP interacts with a virus sensor protein, laboratory of genetics and physiology 2 (LGP2), in the early stage of viral infection of human cells. Next, it induces apoptosis by inhibiting the maturation of miRNAs, thereby upregulating the expression of apoptosis regulatory genes. In this study, we show that TRBP undergoes a functional conversion in the late stage of viral infection. Viral infection resulted in the activation of caspases that proteolytically processed TRBP into two fragments. The N-terminal fragment did not interact with Dicer but interacted with type I interferon (IFN) signaling modulators, such as protein kinase R (PKR) and LGP2, and induced ER stress. The end results were irreversible apoptosis and suppression of IFN signaling. Our results demonstrate that the processing of TRBP enhances apoptosis, reducing IFN signaling during viral infection.
2024-04-19 | GSE234547 | GEO
Project description:Anti-viral innate immunity represents the first line of defense against invading viruses and is key to control viral infections, including the pandemic SARS-CoV-2. Body temperature is an omnipresent variable but was so far neglected when addressing host defense mechanisms and susceptibility to SARS-CoV-2 infection. Here we show that increasing temperature in a 1.5°C window, between 36.5°C and 38°C, strongly increases anti-viral immunity. We show that alternative splicing coupled to nonsense-mediated decay decreases STAT2 expression in colder conditions and suggest that increased STAT2 expression at elevated temperature induces the expression of diverse anti-viral genes. This cascade is activated in a remarkably narrow temperature range below febrile temperature, which reflects individual, circadian and age-dependent body temperature variation. Accordingly, decreased body temperature with ageing correlates with reduced expression of anti-viral genes in older individuals. Using cell culture and in vivo models, we show that higher body temperature indeed reduces SARS-CoV-2 replication, which likely impacts on the different vulnerability of children versus seniors towards severe SARS-CoV-2 infection. Altogether, our data reveal a molecular mechanism, from temperature sensing and pre-mRNA processing to an in vivo phenotype connecting body temperature variation with SARS-CoV-2 replication, thus providing a new paradigm for the regulation of anti-viral innate immunity.
2022-05-31 | GSE193639 | GEO
Project description:Caspase-mediated processing of TRBP regulates apoptosis during viral infection
| PRJNA982029 | ENA
Project description:Caspase-mediated processing of TRBP regulates apoptosis during viral infection
| PRJNA982025 | ENA