nsp12 synthesizes minus strand SARS-CoV-2 genomic RNA complement

Stable Identifier
R-HSA-9694605
Type
Reaction [uncertain]
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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nsp12 synthesizes minus strand SARS-CoV-2 genomic RNA complement
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Virally encoded RNA-dependent RNA polymerase (nsp12, also known as RdRP) is the key component of the replication transcription complex (RTC). SARS-CoV-2-derived nsp12, in complex with nsp7 and nsp8, was shown to have RNA polymerization activity on a poly-U template (Yin et al. 2020). Details of SARS-CoV-2 replication have not yet been elucidated and are inferred from SARS-CoV-1. As SARS-CoV-2 and SARS-CoV-1 are plus strand RNA viruses, nsp12 first synthesizes the complementary minus RNA strand. The purified SARS-CoV-1 nsp12 shows both primer dependent and primer-independent RNA synthesis activities using homopolymeric RNA templates. The catalytic activity of nsp12 is strictly dependent on manganese ions (Mn2+) and primers when the template is a viral-genome-derived RNA representing part of the 3’-UTR of the plus strand with a polyA tail. A 36 nucleotide sequence from the 3’-UTR, predicted to form a stable stem-loop structure, seems to be the minimal cis-acting RNA element required for nsp12 to initiate RNA synthesis (Ahn et al. 2012). The complex of nsp7 and nsp8 confers processivity to nsp12 (Subissi et al. 2014).
Literature References
PubMed ID Title Journal Year
32358203 Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir

Jiang, Y, Wang, X, Shen, DD, Su, H, Tao, SC, Xie, YC, Zhang, Y, Gao, M, Jiang, H, Mao, C, Xu, HE, Zhang, S, Shen, J, Zhou, F, Luan, X, Jiang, HW, Yin, W, Zhao, W, Xu, Y, Shen, Q, Tian, G, Chang, S

Science 2020
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Catalyst Activity

RNA-directed 5'-3' RNA polymerase activity of SARS-CoV-2 gRNA:RTC:RNA primer [double membrane vesicle viral factory outer membrane]

Physical Entity
SARS-CoV-2 gRNA:RTC:RNA primer [double membrane vesicle viral factory outer membrane] (Severe acute respiratory syndrome coronavirus 2)
Activity
RNA-directed 5'-3' RNA polymerase activity (GO:0003968)
This event is regulated
Negatively by
Regulator
SARS-CoV-2 gRNA:RTC:RNA primer:RTC inhibitors [double membrane vesicle viral factory outer membrane] (Severe acute respiratory syndrome coronavirus 2)
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
Orlic-Milacic, M  (2020-08-12)
Reviewed
Acencio, ML  (2020-09-09)
Created
Cook, J  (2020-07-07)
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