2. Academic Validation
  3. De novo assembly of nuclear stress bodies rearranges and enhances NFIL3 to restrain acute inflammatory responses

De novo assembly of nuclear stress bodies rearranges and enhances NFIL3 to restrain acute inflammatory responses

  • Cell. 2025 May 19:S0092-8674(25)00514-8. doi: 10.1016/j.cell.2025.05.003.
Xiao-Qi Liu 1,  Pan Li 2,  Bao-Qing Gao 3,  Heng-Le Zhu 1,  Liang-Zhong Yang 1,  Yang Wang 1,  Yu-Yao Zhang 4,  Hao Wu 1,  Yu-Hang Pan 1,  Lin Shan 1,  Hongtao Yu 5,  Li Yang 4,  Ling-Ling Chen 6
Affiliations

Affiliations

  • 1 State Key Laboratory of RNA Innovation, Science and Engineering, New Cornerstone Science Laboratory, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • 2 State Key Laboratory of RNA Innovation, Science and Engineering, New Cornerstone Science Laboratory, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Department of Cardiology, Changhai Hospital, Shanghai 200433, China.
  • 3 Center for Molecular Medicine, Children's Hospital, Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • 4 Center for Molecular Medicine, Children's Hospital, Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • 5 School of Life Sciences, Westlake University, Hangzhou 310030, Zhejiang, China.
  • 6 State Key Laboratory of RNA Innovation, Science and Engineering, New Cornerstone Science Laboratory, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Academy of Natural Sciences (SANS), Shanghai 200031, China. Electronic address: linglingchen@sibcb.ac.cn.
PMID: 40436014 DOI: 10.1016/j.cell.2025.05.003
Abstract

The membrane-less nuclear stress bodies (nSBs), with satellite III (SatIII) RNAs as the hallmark, are present in primates upon sensing stresses. We report that SatⅢ DNAs, SatⅢ RNAs, and 30 nSB proteins assemble into well-organized structures shortly after stresses. The activated SatⅢ heterochromatin loci rapidly expand, resulting in reduced spatial distance and enhanced expression of adjacent genes, including the transcription suppressor NFIL3, which is known to dampen proinflammatory cytokine production. Rearranging NFIL3 loci within the nSB territory enhances NFIL3 chromatin accessibility and makes NFIL3 promoters more accessible to transcription factors heat shock transcription factor 1 (HSF1) and bromodomain containing 4 (BRD4), which are also recruited to nSBs upon stresses. Human peripheral blood mononuclear cell (PBMC)-derived macrophages under heat shock plus pathogen-associated molecular pattern treatments exhibit increased SatⅢ and NFIL3 expression, the latter of which suppresses key inflammatory cytokines. Importantly, NFIL3 expression positively correlates with SatⅢ activation in septic patients, a process positively correlated to patient survival, highlighting a role of nSBs in restraining inflammatory responses.

Keywords

NFIL3; inflammatory response; nuclear bodies; nuclear stress bodies; satellite III; transcription regulation.

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