The RNA helicase DDX3 promotes IFNB transcription via enhancing IRF-3/p300 holocomplex binding to the IFNB promoter
Abstract The human DEAD-box protein 3 (DDX3) has been reported as a positive regulator and functions in the induction of type I interferon signaling. We elucidated the function of DDX3 in the positive regulation of IFNB production in non-pDC cells. We found that DDX3 regulates virus-induced activati...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-03-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-07876-z |
| _version_ | 1819236893028515840 |
|---|---|
| author | Wilaiporn Saikruang Lena Ang Yan Ping Hiroto Abe Dacquin M. Kasumba Hiroki Kato Takashi Fujita |
| author_facet | Wilaiporn Saikruang Lena Ang Yan Ping Hiroto Abe Dacquin M. Kasumba Hiroki Kato Takashi Fujita |
| author_sort | Wilaiporn Saikruang |
| collection | DOAJ |
| description | Abstract The human DEAD-box protein 3 (DDX3) has been reported as a positive regulator and functions in the induction of type I interferon signaling. We elucidated the function of DDX3 in the positive regulation of IFNB production in non-pDC cells. We found that DDX3 regulates virus-induced activation of IFNB at the level of IRF-3. However, it does not affect conventional innate signaling, including IRF-3 phosphorylation, dimerization, or nuclear translocation of IRF-3, but has some downstream events after IRF-3 phosphorylation. Co-immunoprecipitation analyses revealed that DDX3 interacts with IRF-3 through its DNA-binding domain and promotes IRF-3-mediated IFNB promoter activation. DDX3 does not affect the formation of the IRF-3/p300/CBP complex. Instead, ChIP and EMSA assay revealed that DDX3 promotes the recruitment of IRF-3 and transcriptional co-activator p300/CBP to the IFNB promoter. The ATP binding pocket of DDX3 is involved in this association and is essential for the transcriptional activation. Taken together, our study demonstrates that DDX3 plays an important role in guiding a transcription factor complex formed by antiviral signaling to the target gene promoter. |
| first_indexed | 2024-12-23T13:11:40Z |
| format | Article |
| id | doaj.art-38cc91fcb9724a5ca3f86171bf01ec83 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-23T13:11:40Z |
| publishDate | 2022-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-38cc91fcb9724a5ca3f86171bf01ec832022-12-21T17:45:43ZengNature PortfolioScientific Reports2045-23222022-03-0112111310.1038/s41598-022-07876-zThe RNA helicase DDX3 promotes IFNB transcription via enhancing IRF-3/p300 holocomplex binding to the IFNB promoterWilaiporn Saikruang0Lena Ang Yan Ping1Hiroto Abe2Dacquin M. Kasumba3Hiroki Kato4Takashi Fujita5Division of Integrated Life Science, Graduate School of Biostudies, Kyoto UniversityDivision of Integrated Life Science, Graduate School of Biostudies, Kyoto UniversityDivision of Integrated Life Science, Graduate School of Biostudies, Kyoto UniversityDivision of Integrated Life Science, Graduate School of Biostudies, Kyoto UniversityLaboratory of Regulatory Information, Institute for Frontier Life and Medical Sciences, Kyoto UniversityDivision of Integrated Life Science, Graduate School of Biostudies, Kyoto UniversityAbstract The human DEAD-box protein 3 (DDX3) has been reported as a positive regulator and functions in the induction of type I interferon signaling. We elucidated the function of DDX3 in the positive regulation of IFNB production in non-pDC cells. We found that DDX3 regulates virus-induced activation of IFNB at the level of IRF-3. However, it does not affect conventional innate signaling, including IRF-3 phosphorylation, dimerization, or nuclear translocation of IRF-3, but has some downstream events after IRF-3 phosphorylation. Co-immunoprecipitation analyses revealed that DDX3 interacts with IRF-3 through its DNA-binding domain and promotes IRF-3-mediated IFNB promoter activation. DDX3 does not affect the formation of the IRF-3/p300/CBP complex. Instead, ChIP and EMSA assay revealed that DDX3 promotes the recruitment of IRF-3 and transcriptional co-activator p300/CBP to the IFNB promoter. The ATP binding pocket of DDX3 is involved in this association and is essential for the transcriptional activation. Taken together, our study demonstrates that DDX3 plays an important role in guiding a transcription factor complex formed by antiviral signaling to the target gene promoter.https://doi.org/10.1038/s41598-022-07876-z |
| spellingShingle | Wilaiporn Saikruang Lena Ang Yan Ping Hiroto Abe Dacquin M. Kasumba Hiroki Kato Takashi Fujita The RNA helicase DDX3 promotes IFNB transcription via enhancing IRF-3/p300 holocomplex binding to the IFNB promoter Scientific Reports |
| title | The RNA helicase DDX3 promotes IFNB transcription via enhancing IRF-3/p300 holocomplex binding to the IFNB promoter |
| title_full | The RNA helicase DDX3 promotes IFNB transcription via enhancing IRF-3/p300 holocomplex binding to the IFNB promoter |
| title_fullStr | The RNA helicase DDX3 promotes IFNB transcription via enhancing IRF-3/p300 holocomplex binding to the IFNB promoter |
| title_full_unstemmed | The RNA helicase DDX3 promotes IFNB transcription via enhancing IRF-3/p300 holocomplex binding to the IFNB promoter |
| title_short | The RNA helicase DDX3 promotes IFNB transcription via enhancing IRF-3/p300 holocomplex binding to the IFNB promoter |
| title_sort | rna helicase ddx3 promotes ifnb transcription via enhancing irf 3 p300 holocomplex binding to the ifnb promoter |
| url | https://doi.org/10.1038/s41598-022-07876-z |
| work_keys_str_mv | AT wilaipornsaikruang thernahelicaseddx3promotesifnbtranscriptionviaenhancingirf3p300holocomplexbindingtotheifnbpromoter AT lenaangyanping thernahelicaseddx3promotesifnbtranscriptionviaenhancingirf3p300holocomplexbindingtotheifnbpromoter AT hirotoabe thernahelicaseddx3promotesifnbtranscriptionviaenhancingirf3p300holocomplexbindingtotheifnbpromoter AT dacquinmkasumba thernahelicaseddx3promotesifnbtranscriptionviaenhancingirf3p300holocomplexbindingtotheifnbpromoter AT hirokikato thernahelicaseddx3promotesifnbtranscriptionviaenhancingirf3p300holocomplexbindingtotheifnbpromoter AT takashifujita thernahelicaseddx3promotesifnbtranscriptionviaenhancingirf3p300holocomplexbindingtotheifnbpromoter AT wilaipornsaikruang rnahelicaseddx3promotesifnbtranscriptionviaenhancingirf3p300holocomplexbindingtotheifnbpromoter AT lenaangyanping rnahelicaseddx3promotesifnbtranscriptionviaenhancingirf3p300holocomplexbindingtotheifnbpromoter AT hirotoabe rnahelicaseddx3promotesifnbtranscriptionviaenhancingirf3p300holocomplexbindingtotheifnbpromoter AT dacquinmkasumba rnahelicaseddx3promotesifnbtranscriptionviaenhancingirf3p300holocomplexbindingtotheifnbpromoter AT hirokikato rnahelicaseddx3promotesifnbtranscriptionviaenhancingirf3p300holocomplexbindingtotheifnbpromoter AT takashifujita rnahelicaseddx3promotesifnbtranscriptionviaenhancingirf3p300holocomplexbindingtotheifnbpromoter |