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<p>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 (<i>Tyms</i>) 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, <i>RRP1</i> expression in peripheral blood monocytes negatively correlates with <i>TYMS</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月25日

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  • Yumei Zhou,
  • Mengxuan Li,
  • Ke Jin,
  • Mingyue Wen,
  • Hua Qin,
  • Yue Xu,
  • Chunmei Wang,
  • Xuan Zhang,
  • Xuetao Cao

摘要

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.