The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression
Summary: Many viruses shut off host gene expression to inhibit antiviral responses. Viral proteins and host proteins required for viral replication are typically spared in this process, but the mechanisms of target selectivity during host shutoff remain poorly understood. Using transcriptome-wide an...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-04-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719303936 |
| _version_ | 1819079605507588096 |
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| author | Lea Gaucherand Brittany K. Porter Rachel E. Levene Emma L. Price Summer K. Schmaling Chris H. Rycroft Yuzo Kevorkian Craig McCormick Denys A. Khaperskyy Marta M. Gaglia |
| author_facet | Lea Gaucherand Brittany K. Porter Rachel E. Levene Emma L. Price Summer K. Schmaling Chris H. Rycroft Yuzo Kevorkian Craig McCormick Denys A. Khaperskyy Marta M. Gaglia |
| author_sort | Lea Gaucherand |
| collection | DOAJ |
| description | Summary: Many viruses shut off host gene expression to inhibit antiviral responses. Viral proteins and host proteins required for viral replication are typically spared in this process, but the mechanisms of target selectivity during host shutoff remain poorly understood. Using transcriptome-wide and targeted reporter experiments, we demonstrate that the influenza A virus endoribonuclease PA-X usurps RNA splicing to selectively target host RNAs for destruction. Proximity-labeling proteomics reveals that PA-X interacts with cellular RNA processing proteins, some of which are partially required for host shutoff. Thus, PA-X taps into host nuclear pre-mRNA processing mechanisms to destroy nascent mRNAs shortly after their synthesis. This mechanism sets PA-X apart from other viral host shutoff proteins that target actively translating mRNAs in the cytoplasm. Our study reveals a unique mechanism of host shutoff that helps us understand how influenza viruses suppress host gene expression. : Gaucherand et al. uncover a unique relationship between RNA degradation by the influenza A virus ribonuclease PA-X and host RNA splicing, which allows PA-X to selectively target host RNAs for destruction. Keywords: influenza, host shutoff, PA-X, splicing, CFIm |
| first_indexed | 2024-12-21T19:31:39Z |
| format | Article |
| id | doaj.art-f5a5bbbb824d407b8ae20f0f99e9ef4b |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T19:31:39Z |
| publishDate | 2019-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f5a5bbbb824d407b8ae20f0f99e9ef4b2022-12-21T18:52:42ZengElsevierCell Reports2211-12472019-04-01273776792.e7The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene ExpressionLea Gaucherand0Brittany K. Porter1Rachel E. Levene2Emma L. Price3Summer K. Schmaling4Chris H. Rycroft5Yuzo Kevorkian6Craig McCormick7Denys A. Khaperskyy8Marta M. Gaglia9Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USADepartment of Microbiology & Immunology, Dalhousie University, Halifax, NS, CanadaGraduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USADepartment of Microbiology & Immunology, Dalhousie University, Halifax, NS, CanadaDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USAPaulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA; Computational Research Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USAGraduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USADepartment of Microbiology & Immunology, Dalhousie University, Halifax, NS, Canada; Corresponding authorDepartment of Microbiology & Immunology, Dalhousie University, Halifax, NS, Canada; Corresponding authorGraduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA; Corresponding authorSummary: Many viruses shut off host gene expression to inhibit antiviral responses. Viral proteins and host proteins required for viral replication are typically spared in this process, but the mechanisms of target selectivity during host shutoff remain poorly understood. Using transcriptome-wide and targeted reporter experiments, we demonstrate that the influenza A virus endoribonuclease PA-X usurps RNA splicing to selectively target host RNAs for destruction. Proximity-labeling proteomics reveals that PA-X interacts with cellular RNA processing proteins, some of which are partially required for host shutoff. Thus, PA-X taps into host nuclear pre-mRNA processing mechanisms to destroy nascent mRNAs shortly after their synthesis. This mechanism sets PA-X apart from other viral host shutoff proteins that target actively translating mRNAs in the cytoplasm. Our study reveals a unique mechanism of host shutoff that helps us understand how influenza viruses suppress host gene expression. : Gaucherand et al. uncover a unique relationship between RNA degradation by the influenza A virus ribonuclease PA-X and host RNA splicing, which allows PA-X to selectively target host RNAs for destruction. Keywords: influenza, host shutoff, PA-X, splicing, CFImhttp://www.sciencedirect.com/science/article/pii/S2211124719303936 |
| spellingShingle | Lea Gaucherand Brittany K. Porter Rachel E. Levene Emma L. Price Summer K. Schmaling Chris H. Rycroft Yuzo Kevorkian Craig McCormick Denys A. Khaperskyy Marta M. Gaglia The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression Cell Reports |
| title | The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression |
| title_full | The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression |
| title_fullStr | The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression |
| title_full_unstemmed | The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression |
| title_short | The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression |
| title_sort | influenza a virus endoribonuclease pa x usurps host mrna processing machinery to limit host gene expression |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719303936 |
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