nsp16 acts as a cap 2'-O-methyltransferase to modify SARS-CoV-2 gRNA (plus strand)

Stable Identifier
R-HSA-9694721
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
cytosol, double membrane vesicle viral factory outer membrane
ReviewStatus
5/5
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nsp16 acts as a cap 2'-O-methyltransferase to modify SARS-CoV-2 gRNA (plus strand)
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The function of the non-structural protein nsp16 as a 2'O-methyltransferase that acts in complex with its co-activator nsp10 is conserved in SARS-CoV-2 (Viswanathan et al. 2020).

The genomic and subgenomic mRNAs of SARS-CoV-2 coronavirus, including the plus strand genomic RNA, are presumed to be capped at their 5′ end, based on studies of the mouse hepatitis virus (MHV) (Lai and Stohlman 1981) and the equine torovirus (van Vliet et al. 2002). 2'-O methylation of Cap-0 by SARS-CoV-2 nsp10/nsp16 has been shown, and the process is dependent on the presence of divalent metal cations (Wilamowski et al, 2021; Benoni et al, 2021; Minasov et al, 2021; Viswanathan et al, 2021). The non-structural protein 16 (nsp16) acts as a 2'O-methyltransferase that converts coronavirus cap-0 to cap-1, which was first demonstrated with nsp16 cloned from the feline coronavirus (FCV) (Decroly et al. 2008). Cap-0 represents N7-methyl guanosine connected to the 5′ nucleotide through a 5′ to 5′ triphosphate linkage (also known as m7G cap or m7Gppp cap). Cap-1 is generated by an additional methylation on the 2′O position of the initiating nucleotide, and is also known as m7GpppNm. Non-structural protein 10 (nsp10) acts as an activator of nsp16 and is necessary for cap-1 synthesis (Bouvet et al. 2010, Decroly et al. 2011). Coronavirus RNAs with cap-1 are protected from IFIT-mediated interferon response, as IFITs recognize unmethylated 2'-O RNAs. IFITs are interferon-induced proteins with tetratricopeptide repeats that recognize unmethylated 2'-O RNAs and act to inhibit expression of virally encoded mRNAs (Menachery et al. 2014).
Literature References
PubMed ID Title Journal Year
34578302 Substrate Specificity of SARS-CoV-2 Nsp10-Nsp16 Methyltransferase

Benoni, R, Krafcikova, P, Baranowski, MR, Kowalska, J, Boura, E, Cahová, H

Viruses 2021
34078893 A metal ion orients SARS-CoV-2 mRNA to ensure accurate 2'-O methylation of its first nucleotide

Viswanathan, T, Misra, A, Chan, SH, Qi, S, Dai, N, Arya, S, Martínez-Sobrido, L, Gupta, YK

Nat Commun 2021
34131072 Mn2+ coordinates Cap-0-RNA to align substrates for efficient 2'-O-methyl transfer by SARS-CoV-2 nsp16

Minasov, G, Rosas-Lemus, M, Shuvalova, L, Inniss, NL, Brunzelle, JS, Daczkowski, CM, Hoover, P, Mesecar, AD, Satchell, KJF

Sci Signal 2021
32709886 Structural basis of RNA cap modification by SARS-CoV-2

Viswanathan, T, Arya, S, Chan, SH, Qi, S, Dai, N, Misra, A, Park, JG, Oladunni, F, Kovalskyy, D, Hromas, RA, Martínez-Sobrido, L, Gupta, YK

Nat Commun 2020
33972410 2'-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography

Wilamowski, M, Sherrell, DA, Minasov, G, Kim, Y, Shuvalova, L, Lavens, A, Chard, R, Maltseva, N, Jedrzejczak, R, Rosas-Lemus, M, Saint, N, Foster, IT, Michalska, K, Satchell, KJF, Joachimiak, A

Proc Natl Acad Sci U S A 2021
Participants
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Output
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as an event of
Catalyst Activity

methyltransferase cap1 activity of m7GpppA-capped SARS-CoV-2 genomic RNA (plus strand):RTC [double membrane vesicle viral factory outer membrane]

Physical Entity
m7GpppA-capped SARS-CoV-2 genomic RNA (plus strand):RTC [double membrane vesicle viral factory outer membrane] (Severe acute respiratory syndrome coronavirus 2)
Activity
methyltransferase cap1 activity (GO:0004483)
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
Cross References
Mondo
Authored
Orlic-Milacic, M  (2020-08-12)
Senff-Ribeiro, A  (2020-08-12)
Reviewed
Acencio, ML  (2020-09-09)
Created
Cook, J  (2020-07-07)
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