2. Academic Validation
  3. Characterization of dsRNA binding proteins through solubility analysis identifies ZNF385A as a dsRNA homeostasis regulator

Characterization of dsRNA binding proteins through solubility analysis identifies ZNF385A as a dsRNA homeostasis regulator

  • Nat Commun. 2025 Apr 11;16(1):3433. doi: 10.1038/s41467-025-58704-7.
Na Jiang 1 2 3,  Hekun Yang 1 2 3,  Yi Lei 1 4 5,  Weida Qin 6,  Huifang Xiong 1 2 3,  Kuan Chen 1 2 3,  Kunrong Mei 1 2 3,  Gongyu Li 6,  Xin Mu 7 8 9,  Ruibing Chen 10 11 12
Affiliations

Affiliations

  • 1 School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, China.
  • 2 Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Tianjin, China.
  • 3 State Key Laboratory of Advanced Medical Materials and Devices, Tianjin, China.
  • 4 Tianjin University and Health-Biotech United Group Joint Laboratory of Innovative Drug Development and Translational Medicine, Tianjin University, Tianjin, China.
  • 5 Jinnan Hospital, Tianjin University (Tianjin Jinnan Hospital), Tianjin, China.
  • 6 Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Science, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, China.
  • 7 School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, China. xin_mu@tju.edu.cn.
  • 8 Tianjin University and Health-Biotech United Group Joint Laboratory of Innovative Drug Development and Translational Medicine, Tianjin University, Tianjin, China. xin_mu@tju.edu.cn.
  • 9 Jinnan Hospital, Tianjin University (Tianjin Jinnan Hospital), Tianjin, China. xin_mu@tju.edu.cn.
  • 10 School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, China. rbchen@tju.edu.cn.
  • 11 Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Tianjin, China. rbchen@tju.edu.cn.
  • 12 State Key Laboratory of Advanced Medical Materials and Devices, Tianjin, China. rbchen@tju.edu.cn.
PMID: 40210660 DOI: 10.1038/s41467-025-58704-7
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.

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