2. Academic Validation
  3. Nucleolus assembly impairment leads to two-cell transcriptional repression via NPM1-mediated PRC2 recruitment

Nucleolus assembly impairment leads to two-cell transcriptional repression via NPM1-mediated PRC2 recruitment

  • Nat Struct Mol Biol. 2023 May 18. doi: 10.1038/s41594-023-01003-w.
Dingfeng Li 1 2 3 4,  Ran Cao 3,  Qiaodan Li 3,  Yang Yang 3,  Aihui Tang 3,  Juan Zhang 5 6 7 8 9,  Qiang Liu 10 11 12 13 14 15 16
Affiliations

Affiliations

  • 1 Department of Neurology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
  • 2 Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China.
  • 3 Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
  • 4 Anhui Province Key Laboratory of Biomedical Aging Research, University of Science and Technology of China, Hefei, China.
  • 5 Department of Neurology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. zj2014@ustc.edu.cn.
  • 6 Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China. zj2014@ustc.edu.cn.
  • 7 Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. zj2014@ustc.edu.cn.
  • 8 Anhui Province Key Laboratory of Biomedical Aging Research, University of Science and Technology of China, Hefei, China. zj2014@ustc.edu.cn.
  • 9 CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, China. zj2014@ustc.edu.cn.
  • 10 Department of Neurology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. liuq2012@ustc.edu.cn.
  • 11 Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China. liuq2012@ustc.edu.cn.
  • 12 Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. liuq2012@ustc.edu.cn.
  • 13 Anhui Province Key Laboratory of Biomedical Aging Research, University of Science and Technology of China, Hefei, China. liuq2012@ustc.edu.cn.
  • 14 CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, China. liuq2012@ustc.edu.cn.
  • 15 Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China, Hefei, China. liuq2012@ustc.edu.cn.
  • 16 Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. liuq2012@ustc.edu.cn.
PMID: 37202475 DOI: 10.1038/s41594-023-01003-w
Abstract

The nucleolus is a compartmentalized organelle in eukaryotic cells known to form during embryogenesis, yet how its layered architecture is transformed from homogenous precursor bodies is unclear, and any impacts of this formation on embryonic cell fate determination remain unknown. Here, we demonstrate that lncRNA LoNA tethers granular-component-enriched NPM1 to dense-fibrillar-component-enriched FBL and drives the formation of compartmentalized nucleolus via facilitating liquid-liquid phase separation of those two nucleolar proteins. Phenotypically, LoNA-deficient embryos show developmental arrest at the two-cell (2C) stage. Mechanistically, we demonstrate that LoNA deficiency leads to nucleolar formation failure, resulting in mislocalization and acetylation of NPM1 in the nucleoplasm. Acetylated NPM1 recruits and guides PRC2 complex to 2C genes, where PRC2 complex trimethylates H3K27, leading to transcriptional repression of these genes. Collectively, our findings reveal that lncRNA is required for the establishment of nucleolar structure, and this process has an impact on two-cell embryonic development via 2C transcriptional activation.

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