Viral regulation of host cell biology by hijacking of the nucleolar DNA-damage response
| Autor: | Amanda Woon, Paul J. McMillan, Anthony W. Purcell, Ashley M. Rozario, Toby D. M. Bell, Glenn A. Marsh, Hans J. Netter, Cameron R. Stewart, Gregory W. Moseley, Stephen M. Rawlinson, Tianyue Zhao, Christina L. Rootes, Lin-Fa Wang, Kim G. Lieu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteomics Nucleolus Science General Physics and Astronomy Cell Cycle Proteins Biology General Biochemistry Genetics and Molecular Biology Article Hendra Virus 03 medical and health sciences Viral Proteins Treacle protein Transcription (biology) Gene silencing Humans lcsh:Science Mononegavirales Henipavirus Henipavirus Infections Multidisciplinary Nipah Virus RNA Nuclear Proteins General Chemistry biology.organism_classification Cell biology body regions 030104 developmental biology HEK293 Cells Nucleoproteins Treacle RNA Ribosomal Host-Pathogen Interactions lcsh:Q Cell Nucleolus DNA Damage HeLa Cells |
| Zdroj: | Nature Communications Nature Communications, Vol 9, Iss 1, Pp 1-13 (2018) |
| ISSN: | 2041-1723 |
| Popis: | Recent studies indicate that nucleoli play critical roles in the DNA-damage response (DDR) via interaction of DDR machinery including NBS1 with nucleolar Treacle protein, a key mediator of ribosomal RNA (rRNA) transcription and processing. Here, using proteomics, confocal and single molecule super-resolution imaging, and infection under biosafety level-4 containment, we show that this nucleolar DDR pathway is targeted by infectious pathogens. We find that the matrix proteins of Hendra virus and Nipah virus, highly pathogenic viruses of the Henipavirus genus in the order Mononegavirales, interact with Treacle and inhibit its function, thereby silencing rRNA biogenesis, consistent with mimicking NBS1–Treacle interaction during a DDR. Furthermore, inhibition of Treacle expression/function enhances henipavirus production. These data identify a mechanism for viral modulation of host cells by appropriating the nucleolar DDR and represent, to our knowledge, the first direct intranucleolar function for proteins of any mononegavirus. Many RNA viruses that replicate in the cytoplasm express proteins that localize to nucleoli, but the nucleolar functions remain largely unknown. Here, the authors show that the Henipavirus matrix protein mimics an endogenous Treacle partner of the DNA-damage response, resulting in suppression of rRNA biogenesis. |
| Databáze: | OpenAIRE |
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