Replication transcription complex binds SARS-CoV-2 genomic RNA

Stable Identifier
R-HSA-9694454
Type
Reaction [binding]
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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Replication transcription complex binds SARS-CoV-2 genomic RNA
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The cryo-electron microscopy (cryoEM) structure of the SARS-CoV-2 replication transcription complex (RTC) components nsp7, nsp8 and nsp12, bound to more than two turns of RNA template-product duplex, indicates that the active cleft of nsp12 binds to the first turn of RNA, while two copies of nsp8 bind to opposite sides of the cleft and position the second turn of RNA. Long helical extensions in nsp8 protrude along exiting RNA, forming positively charged "sliding poles". These sliding poles may confer processivity to the RTC (Hillen et al. 2020). Binding of nsp12 to the template RNA is markedly increased by the presence of nsp7 and nsp8 (Yin et al. 2020). Notable structural rearrangements occur in nsp12, nsp8 and nsp7 to accommodate the RNA (Wang et al. 2020).

Based on studies in SARS-CoV-1, the RTC binds to the 3' end of the viral plus strand genomic RNA to initiate synthesis of the complementary minus strand. A 36 nucleotide sequence from the 3’-UTR of the plus strand, predicted to form a stable stem-loop structure, seems to be the minimal cis-acting RNA element required for the viral RNA-directed RNA polymerase (nsp12) to initiate RNA synthesis. The polyA tail also seems to play a role in the initiation of replication of viral genomic RNA (Ahn et al. 2012).
Literature References
PubMed ID Title Journal Year
32438371 Structure of replicating SARS-CoV-2 polymerase

Dienemann, C, Tegunov, D, Cramer, P, Farnung, L, Kokic, G, Hillen, HS

Nature 2020
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
32526208 Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase

Gong, P, Lou, Z, Gao, Y, Zhu, C, Yang, H, Yan, L, Liu, Z, Xu, W, Yang, X, Wang, Q, Liu, F, Rao, Z, Huang, Y, Zhu, Y, Wu, J, Yang, X, Liu, Q, Ji, W, Ge, J, Gao, H, Jiang, B, Fang, X, Wang, H, Guddat, LW, Sun, Q, Mu, A

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
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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