nsp16 acts as a cap 2'-O-methyltransferase to modify SARS-CoV-2 mRNAs

Stable Identifier
R-HSA-9694499
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
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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 subgenomic mRNAs of SARS-CoV-2 coronavirus are presumed to be capped at their 5′ ends, 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. The 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

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

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

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

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

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

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

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

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

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

Proc Natl Acad Sci U S A 2021
Participants
Participates
Catalyst Activity

mRNA (nucleoside-2'-O-)-methyltransferase activity of m7GpppA-SARS-CoV-2 plus strand subgenomic mRNAs:RTC [double membrane vesicle viral factory outer membrane]

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
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