Characterization of dsRNA binding proteins through solubility analysis identifies ZNF385A as a dsRNA homeostasis regulator
Abstract Double-stranded RNA (dsRNA) binding proteins (dsRBPs) play crucial roles in various cellular processes, especially in the innate immune response. Comprehensive characterization of dsRBPs is essential to understand the intricate mechanisms for dsRNA sensing and response. Traditional methods...
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| Language: | English |
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58704-7 |
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| author | Na Jiang Hekun Yang Yi Lei Weida Qin Huifang Xiong Kuan Chen Kunrong Mei Gongyu Li Xin Mu Ruibing Chen |
| author_facet | Na Jiang Hekun Yang Yi Lei Weida Qin Huifang Xiong Kuan Chen Kunrong Mei Gongyu Li Xin Mu Ruibing Chen |
| author_sort | Na Jiang |
| collection | DOAJ |
| description | Abstract Double-stranded RNA (dsRNA) binding proteins (dsRBPs) play crucial roles in various cellular processes, especially in the innate immune response. Comprehensive characterization of dsRBPs is essential to understand the intricate mechanisms for dsRNA sensing and response. Traditional methods have predominantly relied on affinity purification, favoring the isolation of strong dsRNA binders. Here, we adopt the proteome integral solubility alteration (PISA) workflow for characterizing dsRBPs, resulting in the observation of 18 known dsRBPs and the identification of 200 potential dsRBPs. Next, we focus on zinc finger protein 385 A (ZNF385A) and discover that its knockout activates the transcription of interferon-β in the absence of immunogenic stimuli. The knockout of ZNF385A elevates the level of endogenous dsRNAs, especially transcripts associated with retroelements, such as short interspersed nuclear element (SINE), long interspersed nuclear element (LINE), and long terminal repeat (LTR). Moreover, loss of ZNF385A enhances the bioactivity of 5-Aza-2’-deoxycytidine (5-AZA-CdR) and tumor-killing effect of NK cells. Our findings greatly expand the dsRBP reservoir and contribute to the understanding of cellular dsRNA homeostasis. |
| format | Article |
| id | doaj-art-68b793c41d7d4c54a317b155ea559fd7 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-68b793c41d7d4c54a317b155ea559fd72025-08-20T02:17:01ZengNature PortfolioNature Communications2041-17232025-04-0116111910.1038/s41467-025-58704-7Characterization of dsRNA binding proteins through solubility analysis identifies ZNF385A as a dsRNA homeostasis regulatorNa Jiang0Hekun Yang1Yi Lei2Weida Qin3Huifang Xiong4Kuan Chen5Kunrong Mei6Gongyu Li7Xin Mu8Ruibing Chen9School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin UniversitySchool of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin UniversitySchool of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin UniversityTianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Science, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai UniversitySchool of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin UniversitySchool of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin UniversitySchool of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin UniversityTianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Science, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai UniversitySchool of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin UniversitySchool of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin UniversityAbstract Double-stranded RNA (dsRNA) binding proteins (dsRBPs) play crucial roles in various cellular processes, especially in the innate immune response. Comprehensive characterization of dsRBPs is essential to understand the intricate mechanisms for dsRNA sensing and response. Traditional methods have predominantly relied on affinity purification, favoring the isolation of strong dsRNA binders. Here, we adopt the proteome integral solubility alteration (PISA) workflow for characterizing dsRBPs, resulting in the observation of 18 known dsRBPs and the identification of 200 potential dsRBPs. Next, we focus on zinc finger protein 385 A (ZNF385A) and discover that its knockout activates the transcription of interferon-β in the absence of immunogenic stimuli. The knockout of ZNF385A elevates the level of endogenous dsRNAs, especially transcripts associated with retroelements, such as short interspersed nuclear element (SINE), long interspersed nuclear element (LINE), and long terminal repeat (LTR). Moreover, loss of ZNF385A enhances the bioactivity of 5-Aza-2’-deoxycytidine (5-AZA-CdR) and tumor-killing effect of NK cells. Our findings greatly expand the dsRBP reservoir and contribute to the understanding of cellular dsRNA homeostasis.https://doi.org/10.1038/s41467-025-58704-7 |
| spellingShingle | Na Jiang Hekun Yang Yi Lei Weida Qin Huifang Xiong Kuan Chen Kunrong Mei Gongyu Li Xin Mu Ruibing Chen Characterization of dsRNA binding proteins through solubility analysis identifies ZNF385A as a dsRNA homeostasis regulator Nature Communications |
| title | Characterization of dsRNA binding proteins through solubility analysis identifies ZNF385A as a dsRNA homeostasis regulator |
| title_full | Characterization of dsRNA binding proteins through solubility analysis identifies ZNF385A as a dsRNA homeostasis regulator |
| title_fullStr | Characterization of dsRNA binding proteins through solubility analysis identifies ZNF385A as a dsRNA homeostasis regulator |
| title_full_unstemmed | Characterization of dsRNA binding proteins through solubility analysis identifies ZNF385A as a dsRNA homeostasis regulator |
| title_short | Characterization of dsRNA binding proteins through solubility analysis identifies ZNF385A as a dsRNA homeostasis regulator |
| title_sort | characterization of dsrna binding proteins through solubility analysis identifies znf385a as a dsrna homeostasis regulator |
| url | https://doi.org/10.1038/s41467-025-58704-7 |
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