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Targeting Nup358/RanBP2 by a viral protein disrupts stress granule formation
Viruses have evolved mechanisms to modulate cellular pathways to facilitate infection. One such pathway is the formation of stress granules (SG), which are ribonucleoprotein complexes that assemble during translation inhibition following cellular stress. Inhibition of SG assembly has been observed u...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746944/ https://www.ncbi.nlm.nih.gov/pubmed/36455064 http://dx.doi.org/10.1371/journal.ppat.1010598 |
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author | Sadasivan, Jibin Vlok, Marli Wang, Xinying Nayak, Arabinda Andino, Raul Jan, Eric |
author_facet | Sadasivan, Jibin Vlok, Marli Wang, Xinying Nayak, Arabinda Andino, Raul Jan, Eric |
author_sort | Sadasivan, Jibin |
collection | PubMed |
description | Viruses have evolved mechanisms to modulate cellular pathways to facilitate infection. One such pathway is the formation of stress granules (SG), which are ribonucleoprotein complexes that assemble during translation inhibition following cellular stress. Inhibition of SG assembly has been observed under numerous virus infections across species, suggesting a conserved fundamental viral strategy. However, the significance of SG modulation during virus infection is not fully understood. The 1A protein encoded by the model dicistrovirus, Cricket paralysis virus (CrPV), is a multifunctional protein that can bind to and degrade Ago-2 in an E3 ubiquitin ligase-dependent manner to block the antiviral RNA interference pathway and inhibit SG formation. Moreover, the R146 residue of 1A is necessary for SG inhibition and CrPV infection in both Drosophila S2 cells and adult flies. Here, we uncoupled CrPV-1A’s functions and provide insight into its underlying mechanism for SG inhibition. CrPV-1A mediated inhibition of SGs requires the E3 ubiquitin-ligase binding domain and the R146 residue, but not the Ago-2 binding domain. Wild-type but not mutant CrPV-1A R146A localizes to the nuclear membrane which correlates with nuclear enrichment of poly(A)+ RNA. Transcriptome changes in CrPV-infected cells are dependent on the R146 residue. Finally, Nup358/RanBP2 is targeted and degraded in CrPV-infected cells in an R146-dependent manner and the depletion of Nup358 blocks SG formation. We propose that CrPV utilizes a multiprong strategy whereby the CrPV-1A protein interferes with a nuclear event that contributes to SG inhibition in order to promote infection. |
format | Online Article Text |
id | pubmed-9746944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-97469442022-12-14 Targeting Nup358/RanBP2 by a viral protein disrupts stress granule formation Sadasivan, Jibin Vlok, Marli Wang, Xinying Nayak, Arabinda Andino, Raul Jan, Eric PLoS Pathog Research Article Viruses have evolved mechanisms to modulate cellular pathways to facilitate infection. One such pathway is the formation of stress granules (SG), which are ribonucleoprotein complexes that assemble during translation inhibition following cellular stress. Inhibition of SG assembly has been observed under numerous virus infections across species, suggesting a conserved fundamental viral strategy. However, the significance of SG modulation during virus infection is not fully understood. The 1A protein encoded by the model dicistrovirus, Cricket paralysis virus (CrPV), is a multifunctional protein that can bind to and degrade Ago-2 in an E3 ubiquitin ligase-dependent manner to block the antiviral RNA interference pathway and inhibit SG formation. Moreover, the R146 residue of 1A is necessary for SG inhibition and CrPV infection in both Drosophila S2 cells and adult flies. Here, we uncoupled CrPV-1A’s functions and provide insight into its underlying mechanism for SG inhibition. CrPV-1A mediated inhibition of SGs requires the E3 ubiquitin-ligase binding domain and the R146 residue, but not the Ago-2 binding domain. Wild-type but not mutant CrPV-1A R146A localizes to the nuclear membrane which correlates with nuclear enrichment of poly(A)+ RNA. Transcriptome changes in CrPV-infected cells are dependent on the R146 residue. Finally, Nup358/RanBP2 is targeted and degraded in CrPV-infected cells in an R146-dependent manner and the depletion of Nup358 blocks SG formation. We propose that CrPV utilizes a multiprong strategy whereby the CrPV-1A protein interferes with a nuclear event that contributes to SG inhibition in order to promote infection. Public Library of Science 2022-12-01 /pmc/articles/PMC9746944/ /pubmed/36455064 http://dx.doi.org/10.1371/journal.ppat.1010598 Text en © 2022 Sadasivan et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Sadasivan, Jibin Vlok, Marli Wang, Xinying Nayak, Arabinda Andino, Raul Jan, Eric Targeting Nup358/RanBP2 by a viral protein disrupts stress granule formation |
title | Targeting Nup358/RanBP2 by a viral protein disrupts stress granule formation |
title_full | Targeting Nup358/RanBP2 by a viral protein disrupts stress granule formation |
title_fullStr | Targeting Nup358/RanBP2 by a viral protein disrupts stress granule formation |
title_full_unstemmed | Targeting Nup358/RanBP2 by a viral protein disrupts stress granule formation |
title_short | Targeting Nup358/RanBP2 by a viral protein disrupts stress granule formation |
title_sort | targeting nup358/ranbp2 by a viral protein disrupts stress granule formation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746944/ https://www.ncbi.nlm.nih.gov/pubmed/36455064 http://dx.doi.org/10.1371/journal.ppat.1010598 |
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