SARS-CoV-2 nsp1 binds to 40S ribosomal complex

Stable Identifier
R-HSA-9729849
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
cytosol
ReviewStatus
5/5
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SARS-CoV-2 nsp1 binds to 40S ribosomal complex
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SARS-CoV-1 nsp1 induces a near-complete shutdown of host protein translation by both binding to ribosome subunits, blocking canonical mRNA translation, and by endonucleolytic cleavage and subsequent degradation of host mRNAs (Kamitani et al, 2009).

SARS-CoV-2 nsp1 protein binds to the 18S rRNA subunit of the 40S ribosomal complex, which is both part of the 43S pre-initiation complex and the 80S ribosome. Nsp1 binds in the mRNA entrance channel on the 40S subunit, where it would partially overlap with the fully accommodated mRNA. The nsp1 C-terminal domain is necessary and sufficient for translation inhibition. By this mechanism, nsp1 substantially downregulates the innate immune responses (Burke et al, 2021; Slavin et al, 2021; Banerjee et al, 2020; Schubert et al, 2020; Thoms et al, 2020; Yuan et al, 2020; Lapointe et al, 2021).

It appears that translation inhibition is not universal. Functionally related genes, including components of the translation and folding machinery, preferentially escape Nsp1-dependent translation inhibition. Highly translated genes overwhelmingly have 5′ terminal oligopyrimidine (TOP) motifs, suggesting a mechanism for their selective translational response (Rao et al, 2020).

In addition to widespread shutdown of host protein translation, cis-acting RNA hairpin SL1 in the leader sequence of SARS-CoV-2 RNA facilitates evasion of viral RNAs from the nsp1-induced translational suppression (Banerjee et al, 2020; Schubert et al, 2020; Shi et al, 2020; Tidu et al, 2021). Further, the N-terminal domain of nsp1 promotes 40S-mediated viral, but not host, mRNA recognition and translation (Mendez et al, 2021; Wang et al, 2023)
Literature References
PubMed ID Title Journal Year
33479166 Dynamic competition between SARS-CoV-2 NSP1 and mRNA on the human ribosome inhibits translation initiation

Johnson, AG, Grosely, R, Wang, J, Fernández, IS, Puglisi, JD, Lapointe, CP

Proc Natl Acad Sci U S A 2021
32995777 SARS-CoV-2 Nsp1 suppresses host but not viral translation through a bipartite mechanism

Fu, TM, Lieberman, J, Wu, H, Zhang, Y, Shi, M, Fontana, P, Vora, S, Wang, L

bioRxiv 2020
19838190 A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein

Huang, C, Makino, S, Lokugamage, KG, Kamitani, W, Narayanan, K

Nat Struct Mol Biol 2009
32680882 Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2

Cheng, J, Ameismeier, M, Beckmann, R, Hayn, M, Thoms, M, Berninghausen, O, Kirchhoff, F, Buschauer, R, Hirschenberger, M, Becker, T, Denk, T, Sparrer, KMJ, Fröhlich, T, Straub, JH, Mackens-Kiani, T, Koepke, L, Stürzel, CM, Kratzat, H

Science 2020
32908316 SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation

Gurzeler, LA, Ban, N, Jomaa, A, Schubert, K, Karousis, ED, Echeverria, B, Thiel, V, Leibundgut, M, Scaiola, A, Muhlemann, O

Nat Struct Mol Biol 2020
33188728 Nonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA

Lomakin, IB, Park, JJ, Dong, MB, Yuan, S, Wu, S, Hu, Y, Peng, L, Devarkar, SC, Xiong, Y, Chen, S, Shen, Q

Mol Cell 2020
34315815 SARS-CoV-2 infection triggers widespread host mRNA decay leading to an mRNA export block

St Clair, LA, Parker, R, Perera, R, Burke, JM

RNA 2021
34624207 The N-terminal domain of SARS-CoV-2 nsp1 plays key roles in suppression of cellular gene expression and preservation of viral gene expression

Mendez, AS, Ingolia, NT, Hartenian, E, Glaunsinger, BA, Ly, M, González-Sánchez, AM, Cate, JH

Cell Rep 2021
34373319 Targeted in situ cross-linking mass spectrometry and integrative modeling reveal the architectures of three proteins from SARS-CoV-2

Stolovich-Rain, M, Kalisman, N, Baraz, L, Rouvinski, A, Braitbard, M, Friedman, A, Eliyahu, T, Brielle, E, Slavin, M, Wolf, DG, Zohar, K, Linial, M, Schneidman-Duhovny, D, Zamel, J

Proc Natl Acad Sci U S A 2021
33268501 The viral protein NSP1 acts as a ribosome gatekeeper for shutting down host translation and fostering SARS-CoV-2 translation

Kuhn, L, Hammann, P, Tidu, A, Martin, F, Schaeffer, L, Sosnowski, P, Janvier, A, Westhof, E, Eriani, G

RNA 2020
36610391 Structural insights into the activity regulation of full-length non-structural protein 1 from SARS-CoV-2

Kirkpatrick, J, Lage, SZ, Wang, Y, Carlomagno, T

Structure 2023
32995776 Genes with 5' terminal oligopyrimidine tracts preferentially escape global suppression of translation by the SARS-CoV-2 NSP1 protein

Hoskins, I, Ozadam, H, Tonn, T, Cenik, C, Garcia, PD, Rao, S, Cenik, ES

bioRxiv 2020
33080218 SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses

Thai, J, Bruce, EA, Honson, DD, Ollikainen, N, Botten, JW, Miller, ZD, Voorhees, RM, Goldfarb, D, Guttman, M, Schmidt, MM, Chow, A, Blanco, MR, Quinodoz, SA, Majumdar, D, Bhat, P, Lin, AE, Stewart, DG, Banerjee, AK, Loney, C, Rihn, SJ, De Lorenzo, G, Chen, LM

Cell 2020
Participants
Input
Output
Participates
as an event of
Disease
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
Authored
Stephan, R  (2021-05-03)
Reviewed
Messina, F  (2022-02-18)
Created
Stephan, R  (2021-05-03)
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