ArticlePLoS pathogens2014
Cytoplasmic viral RNA-dependent RNA polymerase disrupts the intracellular splicing machinery by entering the nucleus and interfering with Prp8.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 59 citations in OpenAlex.
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- The multiple roles of viral 3DVirulence · 2024Review
- Modulation of nucleotide metabolism by picornaviruses.PLoS pathogens · 2024Article
- Modifying the antiviral innate immune response by selective writing, erasing, and reading of mCell chemical biology · 2024Review
- Multiple functions of the nonstructural protein 3D in picornavirus infection.Frontiers in immunology · 2024Review
- Virus usurps alternative splicing to clear the decks for infection.Virology journal · 2023Review
- Plerixafor and resatorvid inhibit hepatitis B virusFrontiers in cellular and infection microbiology · 2023Article
- The SARS-CoV-2 UTR's Intrudes Host RBP's and Modulates Cellular Splicing.Advances in virology · 2023Article
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- Reovirus μ2 protein modulates host cell alternative splicing by reducing protein levels of U5 snRNP core components.Nucleic acids research · 2022Article
- Genome-Wide Analysis of Alternative Splicing during Host-Virus Interactions in Chicken.Viruses · 2021Article
- IKKε isoform switching governs the immune response against EV71 infection.Communications biology · 2021Article
- Molecular determinants and heterogeneity underlying host response to EV-A71 infection at single-cell resolution.RNA biology · 2021Article
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- Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The primary role of cytoplasmic viral RNA-dependent RNA polymerase (RdRp) is viral genome replication in the cellular cytoplasm. However, picornaviral RdRp denoted 3D polymerase (3D(pol)) also enters the host nucleus, where its function remains unclear. In this study, we describe a novel mechanism of viral attack in which 3D(pol) enters the nucleus through the nuclear localization signal (NLS) and targets the pre-mRNA processing factor 8 (Prp8) to block pre-mRNA splicing and mRNA synthesis. The fingers domain of 3D(pol) associates with the C-terminal region of Prp8, which contains the Jab1/MPN domain, and interferes in the second catalytic step, resulting in the accumulation of the lariat form of the splicing intermediate. Endogenous pre-mRNAs trapped by the Prp8-3D(pol) complex in enterovirus-infected cells were identified and classed into groups associated with cell growth, proliferation, and differentiation. Our results suggest that picornaviral RdRp disrupts pre-mRNA splicing processes, that differs from viral protease shutting off cellular transcription and translation which contributes to the pathogenesis of viral infection.
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