192: The functional analysis of RIG-I-inducible microRNA

Abstract

In mammals, viral infections are detected by innate immune receptors, including Toll-like receptor (TLR) and retinoic acid inducible gene I (RIG-I)-like receptor (RLR), which activate the type I interferon (IFN) system. IFN essentially activates genes encoding antiviral proteins that inhibit various steps of viral replication as well as facilitate the subsequent activation of acquired immune responses. In this study, we investigated the expression of non-coding RNA upon viral infection or RLR activation. Using a microarray, we identified several microRNAs (miRNAs) specifically induced by the activation of RLR signaling. According to miRNA microarray, miR-423-3p was one of the RIG-I-inducible miRNAs. We found that overexpression of miR-423-3p augments expression level of IFN-β upon viral infection. Conversely, introduction of anti-miR-423-3p suppressed expression level of IFN-β upon viral infection. To explore the possible target genes of miR-423-3p, we used three different databases (Target Scan, Micro Cosm, microRNA.org). Among these database, only one gene, Poly(A)-binding protein 1 (PABP1), was overlapped. PABP1 is known as one of the components of stress granules (SGs). Previously we have reported that SGs are important loci to mediate RIG-I signaling. Knockdown and overexpression experiment of PABP1 revealed enhanced and suppressed production of IFN-β respectively. These results suggest that PABP1 acts as a negative regulator of RIG-I mediate signaling and the function of PABP1 is finely regulated by miR-423-3p.