A DNA-sensing-independent role of a nuclear RNA helicase, DHX9, in stimulation of NF-κB-mediated innate immunity against DNA virus infection

Yee Ching Ng, Woo Chang Chung, Hye Ri Kang, Hye Jeong Cho, Eun Byeol Park, Suk Jo Kang, Moon Jung Song

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)9011-9026
Number of pages16
JournalNucleic Acids Research
Volume46
Issue number17
DOIs
Publication statusPublished - 2018 Sep 28

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DNA Virus Infections
RNA Helicases
Nuclear RNA
Innate Immunity
RNA Polymerase II
Dendritic Cells
Adenosine Triphosphatases
DNA
Fibroblasts
Macrophages
Multiprotein Complexes
DNA Viruses
Virus Replication
Nuclear Proteins
Transcriptional Activation
Chromatin
Antiviral Agents
Binding Sites

ASJC Scopus subject areas

  • Genetics

Cite this

A DNA-sensing-independent role of a nuclear RNA helicase, DHX9, in stimulation of NF-κB-mediated innate immunity against DNA virus infection. / Ng, Yee Ching; Chung, Woo Chang; Kang, Hye Ri; Cho, Hye Jeong; Park, Eun Byeol; Kang, Suk Jo; Song, Moon Jung.

In: Nucleic Acids Research, Vol. 46, No. 17, 28.09.2018, p. 9011-9026.

Research output: Contribution to journalArticle

Ng, Yee Ching ; Chung, Woo Chang ; Kang, Hye Ri ; Cho, Hye Jeong ; Park, Eun Byeol ; Kang, Suk Jo ; Song, Moon Jung. / A DNA-sensing-independent role of a nuclear RNA helicase, DHX9, in stimulation of NF-κB-mediated innate immunity against DNA virus infection. In: Nucleic Acids Research. 2018 ; Vol. 46, No. 17. pp. 9011-9026.
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