Rig-I regulates NF-κB activity through binding to Nf-κb1 3′-UTR mRNA

Retinoic acid inducible gene I (RIG-I) senses viral RNAs and triggers innate antiviral responses through induction of type I IFNs and inflammatory cytokines. However, whether RIG-I interacts with host cellular RNA remains undetermined. Here we report that Rig-I interacts with multiple cellular mRNAs, especially Nf-kappa b1. Rig-I is required for NF-kappa B activity via regulating Nf-kappa b1 expression at posttranscriptional levels. It interacts with the multiple binding sites within 3'-UTR of Nf-kappa b1 mRNA. Further analyses reveal that three distinct tandem motifs enriched in the 3'-UTR fragments can be recognized by Rig-I. The 3'-UTR binding with Rig-I plays a critical role in normal translation of Nf-kappa b1 by recruiting the ribosomal proteins [ribosomal protein L13 (Rpl13) and Rpl8] and rRNAs (18S and 28S). Down-regulation of Rig-I or Rpl13 significantly reduces Nf-kappa b1 and 3'-UTR-mediated luciferase expression levels. These findings indicate that Rig-I functions as a positive regulator for NF-kappa B signaling and is involved in multiple biological processes in addition to host antivirus immunity.