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  3. The RNA-binding protein RRP1 brakes macrophage one-carbon metabolism to suppress autoinflammation

The RNA-binding protein RRP1 brakes macrophage one-carbon metabolism to suppress autoinflammation

  • Nat Commun. 2025 Jul 25;16(1):6880. doi: 10.1038/s41467-025-62173-3.
Yumei Zhou # 1 2 3,  Mengxuan Li # 3,  Ke Jin 4,  Mingyue Wen 1 2,  Hua Qin 5,  Yue Xu 6,  Chunmei Wang 1 2,  Xuan Zhang 6,  Xuetao Cao 7 8 9
Affiliations

Affiliations

  • 1 National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China.
  • 2 Department of Immunology, Center for Immunotherapy, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
  • 3 National Key Laboratory of Immunity and Inflammation, Institute of Immunology, Navy Medical University, Shanghai, China.
  • 4 Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
  • 5 Institute of Immunology, College of Life Sciences, Nankai University, Tianjin, China.
  • 6 Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
  • 7 National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China. caoxt@immunol.org.
  • 8 Department of Immunology, Center for Immunotherapy, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. caoxt@immunol.org.
  • 9 Institute of Immunology, College of Life Sciences, Nankai University, Tianjin, China. caoxt@immunol.org.
  • # Contributed equally.
PMID: 40715096 DOI: 10.1038/s41467-025-62173-3
Abstract

RNA-binding proteins (RBP) are important for the initiation and resolution of inflammation, so better understanding of RBP-RNA interactions and their crosstalk with metabolism may provide alternate targets to controlling inflammation. Here we establish global RNA-protein interactome purification (GRPIp) to profile the RBP landscape in inflammatory primary macrophages and identify ribosomal RNA processing 1 (RRP1) as a suppressor of inflammatory innate responses. Mechanistically, RRP1 binds nuclear thymidylate synthetase (Tyms) transcript and decreases TYMS expression post-transcriptionally in inflammatory macrophages, consequently suppressing folate metabolism cycle and inhibiting one-carbon metabolism-driven inflammation. Myeloid-specific RRP1-deficient mice develop severe experimental arthritis with increased pro-inflammatory cytokines and immunologic injury. Meanwhile, in patients with rheumatoid arthritis, RRP1 expression in peripheral blood monocytes negatively correlates with TYMS expression and serum IL-1β levels. Our results thus suggest that RRP1 acts as an anti-inflammatory factor through braking one-carbon metabolism post-transcriptionally, thereby implicating potential strategies for controlling autoinflammation.

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