Interaction of SARS-CoV-2 Nucleocapsid Protein and Human RNA Helicases DDX1 and DDX3X Modulates Their Activities on Double-Stranded RNA

Abstract

The nucleocapsid protein Np of SARS-CoV-2 is involved in the replication, transcription, and packaging of the viral genome, but it also plays a role in the modulation of the host cell innate immunity and inflammation response. Ectopic expression of Np alone was able to induce significant changes in the proteome of human cells. The cellular RNA helicase DDX1 was among the proteins whose levels were increased by Np expression. DDX1 and its related helicase DDX3X were found to physically interact with Np and to increase 2- to 4-fold its affinity for double-stranded RNA in a helicase-independent manner. Conversely, Np inhibited the RNA helicase activity of both proteins. These functional interactions among Np and DDX1 and DDX3X highlight novel possible roles played by these host RNA helicases in the viral life cycle.

RNA Regulatory Networks 2.0

“…The interface between RNA-binding proteins (RBPs) and specific RNA molecules is central to the formation of RNA-protein complexes and condensates [20]. The role of one family of RBPs, the RNA helicases, was studied by Lodola et al in the context of SARS-CoV-2 infection [21]. The authors show that human DDX1 and DDX3X helicases can interact with the viral nucleocapsid protein Np and increase its affinity for double-stranded RNA two-to four-fold in a helicase-independent manner.…”

“…The authors show that human DDX1 and DDX3X helicases can interact with the viral nucleocapsid protein Np and increase its affinity for double-stranded RNA two-to four-fold in a helicase-independent manner. This interaction constitutes a host signal and may contribute to the establishment of SARS-CoV-2 infection in human cells [21]. Turbant et al present a study of another RBP, the bacterial master riboregulatory protein Hfq [22], which is involved in several general aspects of bacterial RNA metabolism, including the regulation of transcriptional efficiency and RNA stability.…”