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

Yumei Zhou, Mengxuan Li, Ke Jin, Mingyue Wen, Hua Qin, Yue Xu, Chunmei Wang, Xuan Zhang and Xuetao Cao ()
Additional contact information
Yumei Zhou: Chinese Academy of Medical Sciences
Mengxuan Li: Navy Medical University
Ke Jin: Zhejiang University School of Medicine
Mingyue Wen: Chinese Academy of Medical Sciences
Hua Qin: Nankai University
Yue Xu: Chinese Academy of Medical Sciences
Chunmei Wang: Chinese Academy of Medical Sciences
Xuan Zhang: Chinese Academy of Medical Sciences
Xuetao Cao: Chinese Academy of Medical Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62173-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62173-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62173-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().