A DNA-sensing-independent role of a nuclear RNA helicase, DHX9, in stimulation of NF-κB-mediated innate immunity against DNA virus infection.
Nucleic Acids Res
; 46(17): 9011-9026, 2018 09 28.
Article
en En
| MEDLINE
| ID: mdl-30137501
ABSTRACT
DExD/H-box helicase 9 (DHX9), or RNA helicase A (RHA), is an abundant multifunctional nuclear protein. Although it was previously reported to act as a cytosolic DNA sensor in plasmacytoid dendritic cells (pDCs), the role and molecular mechanisms of action of DHX9 in cells that are not pDCs during DNA virus infection are not clear. Here, a macrophage-specific knockout and a fibroblast-specific knockdown of DHX9 impaired antiviral innate immunity against DNA viruses, leading to increased virus replication. DHX9 enhanced NF-κB-mediated transactivation in the nucleus, which required its ATPase-dependent helicase (ATPase/helicase) domain, but not the cytosolic DNA-sensing domain. In addition, DNA virus infection did not induce cytoplasmic translocation of nuclear DHX9 in macrophages and fibroblasts. Nuclear DHX9 was associated with a multiprotein complex including both NF-κB p65 and RNA polymerase II (RNAPII) in chromatin containing NF-κB-binding sites. DHX9 was essential for the recruitment of RNAPII rather than NF-κB p65, to the corresponding promoters; this function also required its ATPase/helicase activity. Taken together, our results show a critical role of nuclear DHX9 (as a transcription coactivator) in the stimulation of NF-κB-mediated innate immunity against DNA virus infection, independently of DHX9's DNA-sensing function.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ARN Polimerasa II
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ADN Viral
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FN-kappa B
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ARN Helicasas DEAD-box
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Interacciones Huésped-Patógeno
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Inmunidad Innata
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2018
Tipo del documento:
Article