nsp12 misincorporates a nucleotide in nascent RNA minus strand

Stable Identifier
R-HSA-9682563
Type
Reaction [uncertain]
Species
Homo sapiens
Related Species
Human SARS coronavirus
Compartment
cytosol, double membrane vesicle viral factory outer membrane
ReviewStatus
5/5
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nsp12 misincorporates a nucleotide in nascent RNA minus strand
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In the presence of functional nsp14, which acts as a 3'-to-5' exonuclease, the mutation rate during human SARS coronavirus 1 (SARS-CoV-1) replication is 9 x 10^-7 (9E-7) per nucleotide per replication cycle or 2.2 x 10^-5 (2.2E-5) non-redundant substitutions per nucleotide, which translates into 2-3 nucleotide substitutions for each replicated SARS-CoV-1 genome. When nsp14 is defective, the mutation rate during SARS-CoV-1 replication increases to 1.2 x 10^-5 (1.2E-5) mutations per nucleotide per replication cycle or 3.34 x 10^-4 (3.34E-4) non-redundant substitutions per nucleotide, which translates into 12-23 nucleotide substitutions for each replicated SARS-CoV-1 genome (Eckerle et al. 2010). Here the process is annotated in two steps, nsp12- mediated misincorporation of a base (this reaction) and nsp14-mediated detection and removal of that base (next reaction).
Literature References
PubMed ID Title Journal Year
20463816 Infidelity of SARS-CoV Nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing

Li, K, Becker, MM, Scherbakova, S, Lu, X, Denison, MR, Graham, RL, Eckerle, LD, Halpin, RA, Stockwell, TB, Venter, E, Spiro, DJ, Baric, RS

PLoS Pathog. 2010
Participants
Input
Output
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as an event of
Catalyst Activity

RNA-dependent RNA polymerase activity of SARS coronavirus gRNA:RTC:RNA primer [double membrane vesicle viral factory outer membrane]

Physical Entity
SARS coronavirus gRNA:RTC:RNA primer [double membrane vesicle viral factory outer membrane] (Human SARS coronavirus)
Activity
RNA-dependent RNA polymerase activity (GO:0003968)
This event is regulated
Negatively by
Regulator
SARS coronavirus gRNA:RTC:RNA primer:RTC inhibitors [double membrane vesicle viral factory outer membrane] (Human SARS coronavirus)
Orthologous Events
nsp12 misincorporates a nucleotide in nascent RNA minus strand (Homo sapiens)
Disease
Name Identifier Synonyms
severe acute respiratory syndrome DOID:2945 SARS-CoV infection, SARS
Authored
Orlic-Milacic, M  (2020-04-30)
Reviewed
Acencio, ML  (2020-05-27)
Mazein, A  (2020-05-27)
Created
Orlic-Milacic, M  (2020-04-11)
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