LGP2 virus sensor enhances apoptosis by upregulating apoptosis regulatory genes through TRBP-bound miRNAs during viral infection.

Abstract

During viral infection, viral nucleic acids are detected by virus sensor proteins including toll-like receptor 3 or retinoic acid-inducible gene I-like receptors (RLRs) in mammalian cells. Activation of these virus sensor proteins induces type-I interferon production and represses viral replication. Recently, we reported that an RLR family member, laboratory of genetics and physiology 2 (LGP2), modulates RNA silencing by interacting with an RNA silencing enhancer, TAR-RNA binding protein (TRBP). However, the biological implications remained unclear. Here, we show that LGP2 enhances apoptosis by upregulating apoptosis regulatory genes during viral infection. Sendai virus (SeV) infection increased LGP2 expression approximately 900 times compared to that in non-virus-infected cells. Then, the induced LGP2 interacted with TRBP, resulting in the inhibition of maturation of the TRBP-bound microRNA (miRNA) and its subsequent RNA silencing activity. Gene expression profiling revealed that apoptosis regulatory genes were upregulated during SeV infection: caspases-2, -8, -3 and -7, four cysteine proteases with key roles in apoptosis, were upregulated directly or indirectly through the repression of a typical TRBP-bound miRNA, miR-106b. Our findings may shed light on the mechanism of apoptosis, induced by the TRBP-bound miRNAs through the interaction of TRBP with LGP2, as an antiviral defense system in mammalian cells.