Caspase-Dependent Cleavage of DDX21 Suppresses Host Innate Immunity
Wei Wu, Yang Qu, Shengqing Yu, Sa Wang, Yuncong Yin, Qinfang Liu, Chunchun Meng, Ying Liao, Zaib Ur Rehman, Lei Tan, Cuiping Song, Xusheng Qiu, Weiwei Liu, Chan Ding, Yingjie Sun
Abstract
Innate immunity serves as the first barrier against virus infection. DEAD (Glu-Asp-Ala-Glu) box RNA helicases, originally considered to be involved in RNA processing and RNA unwinding, have been shown to play an important role in antiviral innate immunity. The precise regulation of innate immunity is critical for the host because the aberrant production of cytokines leads to unexpected pathological consequences. Here, we identified that DDX21 was cleaved at D126 by virus infection and treatment with RNA/DNA ligands via the caspase-3/6-dependent pathway. The cytoplasmic cleaved DDX21 negatively regulates the IFN-β signaling pathway by suppressing the formation of the DDX1-DDX21-DHX36 complex. In sum, our data identify DDX21 as a regulator of immune balance and most importantly uncover a potential role of DDX21 cleavage in the innate immune response to virus.