SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation

Schubert, Katharina; Karousis, Evangelos D.; Jomaa, Ahmad; Scaiola, Alain; Echeverria, Blanca; Gurzeler, Lukas-Adrian; Leibundgut, Marc; Thiel, Volker; Mühlemann, Oliver; Ban, Nenad (2020). SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation. Nature structural & molecular biology, 27(10), pp. 959-966. Springer Nature 10.1038/s41594-020-0511-8

[img] Text
s41594-020-0511-8.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (8MB) | Request a copy

The SARS-CoV-2 non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, suppresses host innate immune functions. By combining cryo-electron microscopy and biochemistry, we show that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes, including the 43S pre-initiation complex and the non-translating 80S ribosome. The protein inserts its C-terminal domain into the mRNA channel, where it interferes with mRNA binding. We observe translation inhibition in the presence of Nsp1 in an in vitro translation system and in human cells. Based on the high-resolution structure of the 40S–Nsp1 complex, we identify residues of Nsp1 crucial for mediating translation inhibition. We further show that the full-length 5′ untranslated region of the genomic viral mRNA stimulates translation in vitro, suggesting that SARS-CoV-2 combines global inhibition of translation by Nsp1 with efficient translation of the viral mRNA to allow expression of viral genes.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
08 Faculty of Science > Departement of Chemistry and Biochemistry
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
08 Faculty of Science > Department of Biology > Institute of Cell Biology
08 Faculty of Science > Departement of Chemistry and Biochemistry > NCCR RNA & Disease

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Karousis, Evangelos; Gurzeler, Lukas Adrian; Thiel, Volker Earl and Mühlemann, Oliver

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

1545-9993

Publisher:

Springer Nature

Language:

English

Submitter:

Christina Schüpbach

Date Deposited:

15 Sep 2020 17:13

Last Modified:

10 Oct 2020 01:33

Publisher DOI:

10.1038/s41594-020-0511-8

PubMed ID:

32908316

BORIS DOI:

10.7892/boris.146537

URI:

https://boris.unibe.ch/id/eprint/146537

Actions (login required)

Edit item Edit item
Provide Feedback