The SARS-CoV-2 RNA-protein interactome in infected human cells.

Autor: Schmidt N; Helmholtz Institute for RNA-based Infection Research, Helmholtz-Center for Infection Research, Würzburg, Germany., Lareau CA; School of Medicine, Stanford University, Palo Alto, CA, USA., Keshishian H; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Ganskih S; Helmholtz Institute for RNA-based Infection Research, Helmholtz-Center for Infection Research, Würzburg, Germany., Schneider C; Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany.; Department of Biochemistry, University of Würzburg, Würzburg, Germany., Hennig T; Institute for Virology and Immunobiology, Julius-Maximilians-University Würzburg, Würzburg, Germany., Melanson R; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Werner S; Helmholtz Institute for RNA-based Infection Research, Helmholtz-Center for Infection Research, Würzburg, Germany., Wei Y; Helmholtz Institute for RNA-based Infection Research, Helmholtz-Center for Infection Research, Würzburg, Germany., Zimmer M; Helmholtz Institute for RNA-based Infection Research, Helmholtz-Center for Infection Research, Würzburg, Germany., Ade J; Helmholtz Institute for RNA-based Infection Research, Helmholtz-Center for Infection Research, Würzburg, Germany., Kirschner L; Institute for Virology and Immunobiology, Julius-Maximilians-University Würzburg, Würzburg, Germany., Zielinski S; Helmholtz Institute for RNA-based Infection Research, Helmholtz-Center for Infection Research, Würzburg, Germany., Dölken L; Helmholtz Institute for RNA-based Infection Research, Helmholtz-Center for Infection Research, Würzburg, Germany.; Institute for Virology and Immunobiology, Julius-Maximilians-University Würzburg, Würzburg, Germany., Lander ES; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Biology, MIT, Cambridge, MA, USA.; Department of Systems Biology, Harvard Medical School, Boston, MA, USA., Caliskan N; Helmholtz Institute for RNA-based Infection Research, Helmholtz-Center for Infection Research, Würzburg, Germany.; Faculty of Medicine, University of Würzburg, Würzburg, Germany., Fischer U; Helmholtz Institute for RNA-based Infection Research, Helmholtz-Center for Infection Research, Würzburg, Germany.; Department of Biochemistry, University of Würzburg, Würzburg, Germany., Vogel J; Helmholtz Institute for RNA-based Infection Research, Helmholtz-Center for Infection Research, Würzburg, Germany.; Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany., Carr SA; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Bodem J; Institute for Virology and Immunobiology, Julius-Maximilians-University Würzburg, Würzburg, Germany. jochen.bodem@vim.uni-wuerzburg.de., Munschauer M; Helmholtz Institute for RNA-based Infection Research, Helmholtz-Center for Infection Research, Würzburg, Germany. mathias.munschauer@helmholtz-hiri.de.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2021 Mar; Vol. 6 (3), pp. 339-353. Date of Electronic Publication: 2020 Dec 21.
DOI: 10.1038/s41564-020-00846-z
Abstrakt: 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.
Databáze: MEDLINE
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