Nucleic DHX9 cooperates with STAT1 to transcribe interferon-stimulated genes-Reference-Cited by-同舟云学术

Nucleic DHX9 cooperates with STAT1 to transcribe interferon-stimulated genes

Published:2023-02-03 Issue:5 Volume:9 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Ren Xingxing¹²³^ORCID,Wang Decai¹²^ORCID,Zhang Guorong¹²,Zhou Tingyue¹²^ORCID,Wei Zheng⁴^ORCID,Yang Yi⁴^ORCID,Zheng Yunjiang⁴^ORCID,Lei Xuqiu⁴^ORCID,Tao Wanyin¹²^ORCID,Wang Anmin¹²,Li Mingsong³^ORCID,Flavell Richard A.⁴⁵^ORCID,Zhu Shu¹²⁶⁷^ORCID

Affiliation:

1. Department of Digestive Disease, Division of Life Sciences and Medicine, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, 230001 Hefei, China.

2. Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.

3. Department of Gastroenterology, Third Affiliated Hospital of Guangzhou Medical University, 510145 Guangzhou, China.

4. Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA.

5. Howard Hughes Medical Institute, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA.

6. School of Data Science, University of Science and Technology of China, Hefei 230026, China.

7. Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, China.

Abstract

RNA helicase DHX9 has been extensively characterized as a transcriptional regulator, which is consistent with its mostly nucleic localization. It is also involved in recognizing RNA viruses in the cytoplasm. However, there is no in vivo data to support the antiviral role of DHX9; meanwhile, as a nuclear protein, if and how nucleic DHX9 promotes antiviral immunity remains largely unknown. Here, we generated myeloid-specific and hepatocyte-specific DHX9 knockout mice and confirmed that DHX9 is crucial for host resistance to RNA virus infections in vivo. By additional knockout MAVS or STAT1 in DHX9-deficient mice, we demonstrated that nucleic DHX9 plays a positive role in regulating interferon-stimulated gene (ISG) expression downstream of type I interferon. Mechanistically, upon interferon stimulation, DHX9 is directly bound to STAT1 and recruits Pol II to the ISG promoter region to participate in STAT1-mediated transcription of ISGs. Collectively, these findings uncover an important role for nucleic DHX9 in antiviral immunity.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.add5005

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