SARS-CoV-1 Genome Replication and Transcription

Stable Identifier
R-HSA-9679514
Type
Pathway
Species
Homo sapiens
Related Species
Human SARS coronavirus
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Using the genomic RNA as a template, the coronavirus replicase synthesizes full-length negative-sense antigenome, which in turn serves as a template for the synthesis of new genomic RNA (Masters 2006). The polymerase can also switch template during discontinuous transcription of the genome at specific sites called transcription-regulated sequences, thereby producing a 5'-nested set of negative-sense sgRNAs, which are used as templates for the synthesis of a 3'-nested set of positive-sense sgRNAs (Masters 2006). Although genome replication/transcription is mainly mediated by the viral replicase and confines in the replication-transcription complex (RTC), the involvement of various additional viral and host factors has been implicated. For instance, coronavirus N protein is known to serve as an RNA chaperone and facilitate template switching (Zúñiga et al. 2007, Zúñiga et al. 2010). Importantly, the N protein of SARS-CoV-1 and mouse hepatitis virus (MHV-JHM) is also phosphorylated by the host glycogen synthase kinase 3 (GSK3), and inhibition of GSK3 was shown to inhibit viral replication in Vero E6 cells infected with SARS-CoV-1 (Wu et al. 2009). Additionally, GSK3-mediated phosphorylation of the MHV-JHM N protein recruited an RNA-binding protein DEAD-box helicase 1 (DDX1), which facilitates template read-through, favoring the synthesis of genomic RNA and longer sgRNAs (Wu et al. 2014). Another RNA-binding protein called heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) can also bind tightly to SARS-CoV N protein and potentially regulate viral RNA synthesis (Luo et al. 2005). Host RNA-binding proteins could also bind directly to untranslated regions (UTRs) of the coronavirus genome to modulate replication/transcription, such as zinc finger CCHC-type and RNA-binding motif 1 (ZCRB1) binding to the 5-UTR of IBV (Tan et al. 2012), mitochondrial aconitase binding to the 3' UTR of MHV (Nanda and Leibowitz 2001), and poly(A)-binding protein (PABP) to the poly(A) tail of bovine coronavirus (Spagnolo and Hogue 2000). For review, please refer to Snijder et al. 2016 and Fung and Liu 2019.

Literature References
PubMed ID Title Journal Year
10799579 Host protein interactions with the 3' end of bovine coronavirus RNA and the requirement of the poly(A) tail for coronavirus defective genome replication

Spagnolo, JF, Hogue, BG

J. Virol. 2000
22362731 Binding of the 5'-untranslated region of coronavirus RNA to zinc finger CCHC-type and RNA-binding motif 1 enhances viral replication and transcription

Tan, YW, Hong, W, Liu, DX

Nucleic Acids Res. 2012
19955314 Coronavirus nucleocapsid protein facilitates template switching and is required for efficient transcription

Zúñiga, S, Cruz, JL, Sola, I, Mateos-Gomez, PA, Palacio, L, Enjuanes, L

J. Virol. 2010
11774532 Mitochondrial aconitase binds to the 3'-UTR of mouse hepatitis virus RNA

Nanda, SK, Leibowitz, JL

Adv. Exp. Med. Biol. 2001
15862300 The nucleocapsid protein of SARS coronavirus has a high binding affinity to the human cellular heterogeneous nuclear ribonucleoprotein A1

Luo, H, Chen, Q, Chen, J, Chen, K, Shen, X, Jiang, H

FEBS Lett. 2005
27712628 The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing

Snijder, EJ, Decroly, E, Ziebuhr, J

Adv. Virus Res. 2016
25299332 Nucleocapsid phosphorylation and RNA helicase DDX1 recruitment enables coronavirus transition from discontinuous to continuous transcription

Wu, CH, Chen, PJ, Yeh, SH

Cell Host Microbe 2014
16877062 The molecular biology of coronaviruses

Masters, PS

Adv. Virus Res. 2006
31226023 Human Coronavirus: Host-Pathogen Interaction

Fung, TS, Liu, DX

Annu. Rev. Microbiol. 2019
16979208 Coronavirus nucleocapsid protein is an RNA chaperone

Zúñiga, S, Sola, I, Moreno, JL, Sabella, P, Plana-Durán, J, Enjuanes, L

Virology 2007
19106108 Glycogen synthase kinase-3 regulates the phosphorylation of severe acute respiratory syndrome coronavirus nucleocapsid protein and viral replication

Wu, CH, Yeh, SH, Tsay, YG, Shieh, YH, Kao, CL, Chen, YS, Wang, SH, Kuo, TJ, Chen, DS, Chen, PJ

J. Biol. Chem. 2009
Participants
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Disease
Name Identifier Synonyms
severe acute respiratory syndrome 2945 SARS-CoV infection, SARS
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