The leader RNA of SARS-CoV-2 sequesters polypyrimidine tract binding protein (PTBP1) and influences pre-mRNA splicing in infected cells
Copyright © 2024 Elsevier Inc. All rights reserved..
The large amount of viral RNA produced during infections has the potential to interact with and effectively sequester cellular RNA binding proteins, thereby influencing aspects of post-transcriptional gene regulation in the infected cell. Here we demonstrate that the abundant 5' leader RNA region of SARS-CoV-2 viral RNAs can interact with the cellular polypyrimidine tract binding protein (PTBP1). Interestingly, the effect of a knockdown of PTBP1 protein on cellular gene expression is also mimicked during SARS-CoV-2 infection, suggesting that this protein may be functionally sequestered by viral RNAs. Consistent with this model, the alternative splicing of mRNAs that is normally controlled by PTBP1 is dysregulated during SARS-CoV-2 infection. Collectively, these data suggest that the SARS-CoV-2 leader RNA sequesters the cellular PTBP1 protein during infection, resulting in significant impacts on the RNA biology of the host cell. These alterations in post-transcriptional gene regulation may play a role in SARS-CoV-2 mediated molecular pathogenesis.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:592 |
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Enthalten in: |
Virology - 592(2024) vom: 01. März, Seite 109986 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Altina, Noelia H [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 23.02.2024 Date Revised 09.03.2024 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.virol.2024.109986 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM367807300 |
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520 | |a The large amount of viral RNA produced during infections has the potential to interact with and effectively sequester cellular RNA binding proteins, thereby influencing aspects of post-transcriptional gene regulation in the infected cell. Here we demonstrate that the abundant 5' leader RNA region of SARS-CoV-2 viral RNAs can interact with the cellular polypyrimidine tract binding protein (PTBP1). Interestingly, the effect of a knockdown of PTBP1 protein on cellular gene expression is also mimicked during SARS-CoV-2 infection, suggesting that this protein may be functionally sequestered by viral RNAs. Consistent with this model, the alternative splicing of mRNAs that is normally controlled by PTBP1 is dysregulated during SARS-CoV-2 infection. Collectively, these data suggest that the SARS-CoV-2 leader RNA sequesters the cellular PTBP1 protein during infection, resulting in significant impacts on the RNA biology of the host cell. These alterations in post-transcriptional gene regulation may play a role in SARS-CoV-2 mediated molecular pathogenesis | ||
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700 | 1 | |a Anderson, John R |e verfasserin |4 aut | |
700 | 1 | |a Donaldson, Meghan K |e verfasserin |4 aut | |
700 | 1 | |a Elmegerhi, Suad |e verfasserin |4 aut | |
700 | 1 | |a St Clair, Laura A |e verfasserin |4 aut | |
700 | 1 | |a Perera, Rushika |e verfasserin |4 aut | |
700 | 1 | |a Geiss, Brian J |e verfasserin |4 aut | |
700 | 1 | |a Wilusz, Jeffrey |e verfasserin |4 aut | |
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