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Inhibition of SARS-CoV-2 nucleocapsid protein–RNA interaction by guanosine oligomeric RNA

2023; Oxford University Press; Volume: 173; Issue: 6 Linguagem: Inglês

10.1093/jb/mvad008

1756-2651

Ryoya Sekine, Satsuki Tsuno, Hayato Irokawa, Kazuhiro Sumitomo, Tianxue Han, Yusuke Sato, Seiichi Nishizawa, Kouki Takeda, Shusuke Kuge,

Viral Infections and Immunology Research

Abstract The interaction of the β-coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein with genomic RNA is initiated by specific RNA regions and subsequently induces the formation of a continuous polymer with characteristic structural units for viral formation. We hypothesized that oligomeric RNAs, whose sequences are absent in the 29.9-kb genome sequence of SARS-CoV-2, might affect RNA–N protein interactions. We identified two such hexameric RNAs, In-1 (CCGGCG) and G6 (GGGGGG), and investigated their effects on the small filamentous/droplet-like structures (< a few μm) of N protein–genomic RNA formed by liquid–liquid phase separation. The small N protein structures were sequence-specifically enhanced by In-1, whereas G6 caused them to coalesce into large droplets. Moreover, we found that a guanosine 12-mer (G12, GGGGGGGGGGGG) expelled preexisting genomic RNA from the small N protein structures. The presence of G12 with the genomic RNA suppressed the formation of the small N protein structures, and alternatively apparently altered phase separation to induce the formation of large droplets with unclear phase boundaries. We showed that the N-terminal RNA-binding domain is required for the stability of the small N protein structures. Our results suggest that G12 may be a strong inhibitor of the RNA–N protein interaction.