The SARS-CoV-2 RNA–protein interactome in infected human cells
Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry, we identified up to 104 human proteins that direc...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2021
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| Online Access: | https://hdl.handle.net/1721.1/128950 |
| _version_ | 1826201376743489536 |
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| author | Schmidt, Nora Lareau, Caleb A. Keshishian, Hasmik Ganskih, Sabina Schneider, Cornelius Hennig, Thomas Melanson, Randy Werner, Simone Wei, Yuanjie Zimmer, Matthias Ade, Jens Kirschner, Luisa Zielinski, Sebastian Dölken, Lars Lander, Eric Steven Caliskan, Neva Fischer, Utz Vogel, Jörg Carr, Steven A. Bodem, Jochen Munschauer, Mathias |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Schmidt, Nora Lareau, Caleb A. Keshishian, Hasmik Ganskih, Sabina Schneider, Cornelius Hennig, Thomas Melanson, Randy Werner, Simone Wei, Yuanjie Zimmer, Matthias Ade, Jens Kirschner, Luisa Zielinski, Sebastian Dölken, Lars Lander, Eric Steven Caliskan, Neva Fischer, Utz Vogel, Jörg Carr, Steven A. Bodem, Jochen Munschauer, Mathias |
| author_sort | Schmidt, Nora |
| collection | MIT |
| description | Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry, we identified up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We integrated the SARS-CoV-2 RNA interactome with changes in proteome abundance induced by viral infection and linked interactome proteins to cellular pathways relevant to SARS-CoV-2 infections. We demonstrated by genetic perturbation that cellular nucleic acid-binding protein (CNBP) and La-related protein 1 (LARP1), two of the most strongly enriched viral RNA binders, restrict SARS-CoV-2 replication in infected cells and provide a global map of their direct RNA contact sites. Pharmacological inhibition of three other RNA interactome members, PPIA, ATP1A1, and the ARP2/3 complex, reduced viral replication in two human cell lines. The identification of host dependency factors and defence strategies as presented in this work will improve the design of targeted therapeutics against SARS-CoV-2. |
| first_indexed | 2024-09-23T11:50:37Z |
| format | Article |
| id | mit-1721.1/128950 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:50:37Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1289502022-10-01T06:25:14Z The SARS-CoV-2 RNA–protein interactome in infected human cells Schmidt, Nora Lareau, Caleb A. Keshishian, Hasmik Ganskih, Sabina Schneider, Cornelius Hennig, Thomas Melanson, Randy Werner, Simone Wei, Yuanjie Zimmer, Matthias Ade, Jens Kirschner, Luisa Zielinski, Sebastian Dölken, Lars Lander, Eric Steven Caliskan, Neva Fischer, Utz Vogel, Jörg Carr, Steven A. Bodem, Jochen Munschauer, Mathias Massachusetts Institute of Technology. Department of Biology Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry, we identified up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We integrated the SARS-CoV-2 RNA interactome with changes in proteome abundance induced by viral infection and linked interactome proteins to cellular pathways relevant to SARS-CoV-2 infections. We demonstrated by genetic perturbation that cellular nucleic acid-binding protein (CNBP) and La-related protein 1 (LARP1), two of the most strongly enriched viral RNA binders, restrict SARS-CoV-2 replication in infected cells and provide a global map of their direct RNA contact sites. Pharmacological inhibition of three other RNA interactome members, PPIA, ATP1A1, and the ARP2/3 complex, reduced viral replication in two human cell lines. The identification of host dependency factors and defence strategies as presented in this work will improve the design of targeted therapeutics against SARS-CoV-2. 2021-01-04T21:51:50Z 2021-01-04T21:51:50Z 2020-12 2020-07 2021-01-04T18:34:15Z Article http://purl.org/eprint/type/JournalArticle 2058-5276 https://hdl.handle.net/1721.1/128950 Schmidt, Nora et al. "The SARS-CoV-2 RNA–protein interactome in infected human cells." Nature Microbiology (December 2020): doi.org/10.1038/s41564-020-00846-z. © 2020 The Author(s) en http://dx.doi.org/10.1038/s41564-020-00846-z Nature Microbiology Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Schmidt, Nora Lareau, Caleb A. Keshishian, Hasmik Ganskih, Sabina Schneider, Cornelius Hennig, Thomas Melanson, Randy Werner, Simone Wei, Yuanjie Zimmer, Matthias Ade, Jens Kirschner, Luisa Zielinski, Sebastian Dölken, Lars Lander, Eric Steven Caliskan, Neva Fischer, Utz Vogel, Jörg Carr, Steven A. Bodem, Jochen Munschauer, Mathias The SARS-CoV-2 RNA–protein interactome in infected human cells |
| title | The SARS-CoV-2 RNA–protein interactome in infected human cells |
| title_full | The SARS-CoV-2 RNA–protein interactome in infected human cells |
| title_fullStr | The SARS-CoV-2 RNA–protein interactome in infected human cells |
| title_full_unstemmed | The SARS-CoV-2 RNA–protein interactome in infected human cells |
| title_short | The SARS-CoV-2 RNA–protein interactome in infected human cells |
| title_sort | sars cov 2 rna protein interactome in infected human cells |
| url | https://hdl.handle.net/1721.1/128950 |
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