The SARS-unique domain (SUD) of SARS-CoV and SARS-CoV-2 interacts with human Paip1 to enhance viral RNA translation.

Lei, Jian; Ma-Lauer, Yue; Han, Yinze; Thoms, Matthias; Buschauer, Robert; Jores, Joerg; Thiel, Volker; Beckmann, Roland; Deng, Wen; Leonhardt, Heinrich; Hilgenfeld, Rolf; von Brunn, Albrecht (2021). The SARS-unique domain (SUD) of SARS-CoV and SARS-CoV-2 interacts with human Paip1 to enhance viral RNA translation. The EMBO journal, 40(11), e102277. EMBO Press 10.15252/embj.2019102277

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The ongoing outbreak of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) demonstrates the continuous threat of emerging coronaviruses (CoVs) to public health. SARS-CoV-2 and SARS-CoV share an otherwise non-conserved part of non-structural protein 3 (Nsp3), therefore named as "SARS-unique domain" (SUD). We previously found a yeast-2-hybrid screen interaction of the SARS-CoV SUD with human poly(A)-binding protein (PABP)-interacting protein 1 (Paip1), a stimulator of protein translation. Here, we validate SARS-CoV SUD:Paip1 interaction by size-exclusion chromatography, split-yellow fluorescent protein, and co-immunoprecipitation assays, and confirm such interaction also between the corresponding domain of SARS-CoV-2 and Paip1. The three-dimensional structure of the N-terminal domain of SARS-CoV SUD ("macrodomain II", Mac2) in complex with the middle domain of Paip1, determined by X-ray crystallography and small-angle X-ray scattering, provides insights into the structural determinants of the complex formation. In cellulo, SUD enhances synthesis of viral but not host proteins via binding to Paip1 in pBAC-SARS-CoV replicon-transfected cells. We propose a possible mechanism for stimulation of viral translation by the SUD of SARS-CoV and SARS-CoV-2.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Veterinary Bacteriology

UniBE Contributor:

Jores, Jörg and Thiel, Volker Earl

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1460-2075

Publisher:

EMBO Press

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

13 Jul 2021 09:34

Last Modified:

18 Jul 2021 03:06

Publisher DOI:

10.15252/embj.2019102277

PubMed ID:

33876849

Uncontrolled Keywords:

coronavirus eukaryotic translation initiation factors macrodomain protein synthesis virus-host interactions

BORIS DOI:

10.48350/156608

URI:

https://boris.unibe.ch/id/eprint/156608

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