DEAD (
Glu-Asp-Ala-Glu) box
RNA helicases have been proven to contribute to
antiviral innate immunity. The DDX21
RNA helicase was identified as a
nuclear protein involved in rRNA processing and
RNA unwinding. DDX21 was also proven to be the scaffold
protein in the complex of DDX1-DDX21-DHX36, which senses double-strand
RNA and initiates downstream innate immunity. Here, we identified that DDX21 undergoes
caspase-dependent cleavage after
virus infection and treatment with
RNA/
DNA ligands, especially for RNA virus and
ligands.
Caspase-3/6 cleaves DDX21 at D126 and promotes its translocation from the nucleus to the cytoplasm in response to
virus infection. The cytoplasmic cleaved DDX21 negatively regulates the
interferon beta (IFN-β) signaling pathway by suppressing the formation of the DDX1-DDX21-DHX36 complex. Thus, 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. IMPORTANCE 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.