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.