CNBP binds SARS-CoV-2 G-rich RNA

Stable Identifier
R-HSA-9759709
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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CNBP binds SARS-CoV-2 G-rich RNA
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The CCHC-type zinc finger nucleic acid-binding protein (also known as cellular nucleic acid-binding protein CNBP, ZNF9) is a single-stranded (ss) DNA or RNA binding protein that preferentially binds guanine (G)-rich elements in the target nucleic acid sequences. G-rich DNA or RNA can fold into non-canonical four-stranded secondary structures named G-quadruplexes (G4). CNBP was shown to regulate gene expression both at transcriptional and translational levels through unfolding G4 structures (Benhalevy D et al. 2017; David AP et al. 2019). G4 motifs in DNA and RNA have been found in genomes of various species (Marsico G et al. 2019; Wu F et al. 2021). Human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also harbor G4 in their genomes (Cui H & Zhang L 2020; Ji D et al. 2021; Zhao C et al. 2021; Bezzi G et al. 2021; Miclot T et al. 2021). Enhanced crosslinking and immunoprecipitation (eCLIP) data suggest that CNBP directly binds to SARS-CoV-2 gRNA in SARS-CoV-2-infected human hepatocyte-derived cellular carcinoma Huh-7 cells (Schmidt N et al. 2021). Electrophoretic mobility shift assays (EMSAs) showed that CNBP can bind to several G4s identified within the positive-sense and negative-sense gRNA strands of SARS-CoV-2 (Bezzi G et al. 2021). Circular dichroism spectroscopy showed that CNBP is capable of unfolding the G4s structures in SARS-CoV-2 gRNA. CNBP deficiency in SARS-CoV-2-infected Huh-7 cells resulted in elevated levels of intracellular viral RNA (Schmidt N et al. 2021). These data suggest that CNBP may act as a direct regulator of SARS-CoV-2 viral replication (Bezzi G et al. 2021).

This Reactome event shows CNBP binding to G-rich elements in SARS-CoV-2 gRNA. The RNA binding activity of CNBP is downregulated by PRMT1-mediated methylation at R25 and R27 (Wei HM et al. 2014).

Literature References
PubMed ID Title Journal Year
33349665 The SARS-CoV-2 RNA-protein interactome in infected human cells

Schmidt, N, Lareau, CA, Keshishian, H, Ganskih, S, Schneider, C, Hennig, T, Melanson, R, Werner, S, Wei, Y, Zimmer, M, Ade, J, Kirschner, L, Zielinski, S, Dölken, L, Lander, ES, Caliskan, N, Fischer, U, Vogel, J, Carr, SA, Bodem, J, Munschauer, M

Nat Microbiol 2021
33807682 CNBP Binds and Unfolds In Vitro G-Quadruplexes Formed in the SARS-CoV-2 Positive and Negative Genome Strands

Bezzi, G, Piga, EJ, Binolfi, A, Armas, P

Int J Mol Sci 2021
Participants
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
MeR25,27-CNBP [cytosol] (Homo sapiens)
Authored
Shamovsky, V  (2021-10-27)
Reviewed
Messina, F  (2022-02-18)
Created
Shamovsky, V  (2021-12-10)
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