Search

RIG-I-like receptor (RLR) plays a pivotal role in the detection of invading pathogens to initiate type I interferon (IFN) gene transcription. Since aberrant IFN production is harmful, RLR signaling is strictly regulated. However, the regulatory mechanisms are not fully understood. By expression cloning, we identified Pumilio proteins, PUM1 and PUM2, as candidate positive regulators of RIG-I signaling. Overexpression of Pumilio proteins and their knockdown augmented and diminished IFN-β promoter activity induced by Newcastle disease virus (NDV), respectively. Both proteins showed a specific association with LGP2, but not with RIG-I or MDA5. Furthermore, all of these components were recruited to NDV-induced antiviral stress granules. Interestingly, biochemical analyses revealed that Pumilio increased double-stranded (ds) RNA binding affinity of LGP2; however, Pumilio was absent in the dsRNA-LGP2 complex, suggesting that Pumilio facilitates viral RNA recognition by LGP2 through its chaperon-like function. Collectively, our results demonstrate an unknown function of Pumilio in viral recognition by LGP2., Author Summary Mammals utilize innate immune system to counteract viral infections. The host pattern-recognition receptors, such as RIG-I-like receptors (RLRs), sense invading pathogens and initiate innate immune responses. RLRs are composed of three RNA helicases, RIG-I, MDA5 and LGP2, and detect a series of RNA viruses, such as influenza or hepatitis C virus, in the cytoplasm. Upon RNA virus infection, RLRs transmit signals through mitochondrial adaptor protein, IPS-1, to activate transcription factor IRF-3/7, resulting in the production of type I interferon (IFN). Type I IFN plays a crucial role in innate immune system by inducing a hundreds of interferon-stimulated genes and its induction is tightly controlled at transcriptional and translational steps. Pumilio proteins are originally identified as translational repressor through direct binding to specific sequence motifs in the 3′ untranslated regions of specific mRNA, and regulate critical biological processes, such as development and differentiation. In this report, we identified human Pumilio proteins, PUM1 and PUM2, as candidate regulators of IFN signaling. Our results demonstrated an unknown function of Pumilio in viral recognition by LGP2.