The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Clinically observed deletions in SARS-CoV-2 Nsp1 affect protein stability and its ability to inhibit translation
Open accessPreprint — published as 10.1002/1873-3468.14354
Abstract
Summary: Nonstructural protein 1 (Nsp1) is a major pathogenicity factor of SARS-CoV-2. It inhibits host-cell translation, primarily through a direct interaction between its C-terminal domain and the mRNA entry channel of the 40S small ribosomal subunit, with an N-terminal β-barrel domain fine-tuning the inhibition and promoting selective translation of viral mRNA. SARS-CoV-2 nsp1 is a target of recurring deletions, some of which are associated with altered COVID-19 disease progression. To provide the biochemical basis for this, it is essential to characterize the efficiency of translational inhibition by the said protein variants. Here, we use an in vitro translation system to investigate the translation inhibition capacity of a series of clinically observed Nsp1 deletion variants. We find that a frequently observed deletion of residues 79-89 destabilized the N-terminal domain (NTD) and severely reduced the capacity of Nsp1 to inhibit translation. Interestingly, shorter deletions in the same region have been reported to effect the type I interferon response but did not affect translation inhibition, indicating a possible translation-independent role of the Nsp1 NTD in interferon response modulation. Taken together, our data provide a mechanistic basis for understanding how deletions in Nsp1 influence SARS-CoV-2 induction of interferon response and COVID-19 progression.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Flagged first, then by citations
Research works printed but not linked: 37
- 10.1016/j.antiviral.2013.10.013 · DOI
- 10.1016/bs.aivir.2018.01.001 · DOI
- 10.1038/s41586-020-2008-3 · DOI · Paper page
- 10.1016/S0140-6736(20)30154-9 · DOI
- 10.1016/S0140-6736(20)30183-5 · DOI · Paper page
- 10.1016/S0140-6736(20)302518 · DOI
- 2020, Coronavirus RNA Proofreading: Molecular Basis and Therapeutic Targeting, Mol Cell, 80, 1136, 10.1016/j.molcel.2020.11.048 · DOI · Paper page
- 10.1371/journal.ppat.0030109 · DOI
- 10.1073/pnas.0603144103 · DOI
- 10.1038/nsmb.1680 · DOI
- 10.1128/JVI.01958-12 · DOI
- 10.1128/JVI.02472-07 · DOI
- Shen, Z. , Zhang, G. , Yang, Y. , Li, M. , Yang, S. , and Peng, G. (2021) Lysine 164 is critical for SARS-CoV-2 Nsp1 inhibition of host gene expression. J Gen Virol 102 · DOI
- Lapointe, C. P. , Grosely, R. , Johnson, A. G. , Wang, J. , Fernandez, I. S. , and Puglisi, J. D. (2021) Dynamic competition between SARS-CoV-2 NSP1 and mRNA on the human ribosome inhibits translation initiation. Proc Natl Acad Sci U S A 118 · DOI
- 10.1016/j.molcel.2020.10.034 · DOI
- 10.1126/science.abc8665 · DOI
- 2020, SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation, Nat Struct Mol Biol, 27, 959, 10.1038/s41594-020-0511-8 · DOI
- Mendez, A. S. , Ly, M. , Gonzalez-Sanchez, A. M. , Hartenian, E. , Ingolia, N. T. , Cate, J. H. , and Glaunsinger, B. A. (2021) The N-terminal domain of SARS-CoV-2 nsp1 plays key roles in suppression of cellular gene expression and preservation of viral gene expression. Cell Rep, 109841 · DOI
- 10.1016/j.crviro.2021.100007 · DOI
- Slavin, M. , Zamel, J. , Zohar, K. , Eliyahu, T. , Braitbard, M. , Brielle, E. , Baraz, L. , Stolovich-Rain, M. , Friedman, A. , Wolf, D. G. , Rouvinski, A. , Linial, M. , Schneidman-Duhovny, D. , and Kalisman, N. (2021) Targeted in situ cross-linking mass spectrometry and integrative modeling reveal the architectures of three proteins from SARS-CoV-2. Proc Natl Acad Sci U S A 118 · DOI
- Tidu, A. , Janvier, A. , Schaeffer, L. , Sosnowski, P. , Kuhn, L. , Hammann, P. , Westhof, E. , Eriani, G. , and Martin, F. (2020) The viral protein NSP1 acts as a ribosome gatekeeper for shutting down host translation and fostering SARS-CoV-2 translation. RNA · DOI
- 10.1128/JVI.01700-12 · DOI
- 2021, SARS-CoV-2 genetic diversity in Venezuela: Predominance of D614G variants and analysis of one outbreak, PLoS One, 16, e0247196, 10.1371/journal.pone.0247196 · DOI
- 10.3389/fmicb.2020.01800 · DOI
- 10.1016/j.chom.2021.01.015 · DOI
- 10.1186/s12967-020-02507-5 · DOI
- Clark, L. K. , Green, T. J. , and Petit, C. M. (2021) Structure of Nonstructural Protein 1 from SARS-CoV-2. J Virol 95 · DOI
- 10.1128/JVI.01939-06 · DOI
- 10.1016/j.ab.2004.04.031 · DOI
- Gordon, D. E. , Jang, G. M. , Bouhaddou, M. , Xu, J. , Obernier, K. , White, K. M. , O’Meara, M. J. , Rezelj, V. V. , Guo, J. Z. , Swaney, D. L. , Tummino, T. A. , Huettenhain, R. , Kaake, R. M. , Richards, A. L. , Tutuncuoglu, B. , Foussard, H. , Batra, J. , Haas, K. , Modak, M. , Kim, M. , Haas, P. , Polacco, B. J. , Braberg, H. , Fabius, J. M. , Eckhardt, M. , Soucheray, M. , Bennett, M. J. , Cakir, M. , McGregor, M. J. , Li, Q. , Meyer, B. , Roesch, F. , Vallet, T. , Mac Kain, A. , Miorin, L. , Moreno, E. , Naing, Z. Z. C. , Zhou, Y. , Peng, S. , Shi, Y. , Zhang, Z. , Shen, W. , Kirby, I. T. , Melnyk, J. E. , Chorba, J. S. , Lou, K. , Dai, S. A. , Barrio-Hernandez, I. , Memon, D. , Hernandez-Armenta, C. , Lyu, J. , Mathy, C. J. P. , Perica, T. , Pilla, K. B. , Ganesan, S. J. , Saltzberg, D. J. , Rakesh, R. , Liu, X. , Rosenthal, S. B. , Calviello, L. , Venkataramanan, S. , Liboy-Lugo, J. , Lin, Y. , Huang, X. P. , Liu, Y. , Wankowicz, S. A. , Bohn, M. , Safari, M. , Ugur, F. S. , Koh, C. , Savar, N. S. , Tran, Q. D. , Shengjuler, D. , Fletcher, S. J. , O’Neal, M. C. , Cai, Y. , Chang, J. C. J. , Broadhurst, D. J. , Klippsten, S. , Sharp, P. P. , Wenzell, N. A. , Kuzuoglu, D. , Wang, H. Y. , Trenker, R. , Young, J. M. , Cavero, D. A. , Hiatt, J. , Roth, T. L. , Rathore, U. , Subramanian, A. , Noack, J. , Hubert, M. , Stroud, R. M. , Frankel, A. D. , Rosenberg, O. S. , Verba, K. A. , Agard, D. A. , Ott, M. , Emerman, M. , Jura, N. , von Zastrow, M. , Verdin, E. , Ashworth, A. , Schwartz, O. , d’Enfert, C. , Mukherjee, S. , Jacobson, M. , Malik, H. S. , Fujimori, D. G. , Ideker, T. , Craik, C. S. , Floor, S. N. , Fraser, J. S. , Gross, J. D. , Sali, A. , Roth, B. L. , Ruggero, D. , Taunton, J. , Kortemme, T. , Beltrao, P. , Vignuzzi, M. , Garcia-Sastre, A. , Shokat, M. , Shoichet, B. K. , and Krogan, N. J. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature · DOI · Paper page
- 10.1093/nar/gkp665 · DOI
- 10.1261/rna.825008 · DOI
- 10.1006/abio.1993.1284 · DOI
- 10.1002/0471140864.ps2809s79 · DOI
- 10.1371/journal.pcbi.1005659 · DOI · Paper page
- 10.1002/pro.3235 · DOI · Paper page
- 10.1093/bioinformatics/19.2.311 · DOI
Metadata
- Authors
- Kumar, P., Schexnaydre, E., Rafie, K., Terenin, I., Hauryliuk, V., & Carlson, L.-A.
- Affiliations
- Umeå University (SE)
- Lomonosov Moscow State University (RU)
- Lund University (SE)
- Corresponding author
- Hauryliuk, Vasili
- Carlson, Lars-Anders
- Venue
- FEBS Letters
- Publisher
- openRxiv
- Published
- 2021-11-04
- Volume
- 596
- Issue
- 9
- Pages
- 1203-1213
- ISSN
- 0014-5793 (ISSN-L)
- PMC
- PMC9081967
- OpenAlex
- W4224126479
- Cited by
- 9
- References
- 1
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 1 · 2022: 1
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- FEBS Letters (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DiVA at Umeå University (Umeå University) (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Kempe Foundation
- Human Frontier Science Program (CDA00047/2017‐C)
- Eesti Teadusagentuur (PRG335)
- Cancerfonden (20 0872 Pj)
- Knut och Alice Wallenbergs Stiftelse (2020.0037)
- Vetenskapsrådet (2017-03783, 2021-01146)
- Umeå Universitet
- Kempestiftelserna (JCK‐1723.2)
- Wallenberg Centre for Molecular and Translational Medicine
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS-CoV-2, Nsp1, NS1 protein, N-terminal domain, protein deletion, protein synthesis inhibition, 40S ribosome, 5' untranslated region, protein thermal stability, protein structure prediction
- MeSH terms
- COVID-19, SARS-CoV-2, Humans, Ribosomes, Protein Biosynthesis, Viral Nonstructural Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
