Non-structural protein 1 of influenza viruses inhibits rapid mRNA degradation mediated by double-stranded RNA-binding protein, staufen1

• The N-terminal RNA-binding domain of NS1 is sufficient for binding to Stau1.
• NS1 inhibits staufen1-mediated mRNA decay.
• NS1 promotes the dissociation of Upf1 from staufen1-containing complex.
• We report a new molecular mechanism regulated by host–viral interaction.

Although non-structural protein 1 (NS1) of influenza viruses is not essential for virulence, this protein is involved in host–virus interactions, viral replication, and translation. In particular, NS1 is known to interact with the host protein, staufen1 (Stau1). This interaction is important for efficient viral replication. However, the underlying molecular mechanism by which NS1 influences the viral life cycle remains obscure. Here, we show using immunoprecipitation and artificial tethering that the N-terminus of NS1, NS1(1-73), interacts with Stau1, blocks the Stau1–Upf1 interaction, and consequently inhibits the efficiency of Stau1-mediated mRNA decay (SMD), but not nonsense-mediatedmRNA decay (NMD). The regulation of SMD efficiency by NS1 may contribute to building a more favorable cellular environment for viral replication.Structured summary of protein interactionsSTAU1-55physically interacts with UPF1 by anti tag-coimmunoprecipitation (View interaction)NS1physically interacts with STAU1-55 by anti tag-coimmunoprecipitation (View interaction)