Meta-Biol

• Pathways

SARS-CoV-2 nucleocapsid protein (N) can undergo liquid-liquid phase separation (LLPS) with RNA (Wu Y et al. 2021; Wang S et al. 2021; Cubuk J et al. 2021; Lu S et al. 2021). The C-terminal dimerization domain (CTD) of viral N is essential for LLPS (Wu Y et al. 2021; Wang S et al. 2021). Acetylation of viral N at K375, a motif that is adjacent to the CTD, reduced LLPS and its ability to bind RNA (Wang S et al. 2021). Host CREB-binding protein (CREBBP, CBP) mediated acetylation of N at K375 upon co-expression of tagged proteins in human embryonic kidney 293T cells (HEK293T cells), while CREBBP deficiency caused by small interfering RNA (siRNA) inhibited N acetylation (Wang S et al. 2021). Further, SARS-CoV-2 N:RNA LLPS recruited mitochondrial antiviral-signaling protein (MAVS) (Wang S et al. 2021), TGF-beta-activated kinase 1 (TAK1) and IκB kinase (IKK) complexes (Wu Y et al. 2021). The interaction with MAVS supressed MAVS downstream signaling, while N binding to TAK1 or IKBKB enhanced NB-kappaM activation. CTD of N was essential for these interactions (Wu Y et al. 2021; Wang S et al. 2021). The data suggest that acetylation of viral N at K375 abrogates its LLPS and the N-mediated modulation of host antiviral responses.