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<p>Nuclear condensates (NCs) are membraneless organelles that enable spatial and functional compartmentalization in the nucleus. Yet, the components and functional co-organization of NCs have been poorly studied. Here, we used PhastID to explore the proximal interactome of 18 NCs in HeLa cells. Our data revealed the organizational flow of gene control among these NCs. Crucially, we developed an algorithm to dissect the intricate internal relations of NCs. This algorithm led to key discoveries: the identification of an uncharacterized BUD13 condensate, and the recognition of specific co-organizations between nuclear gems and Cajal bodies for telomerase maturation, and between nuclear gems and histone locus bodies for histone gene pre-mRNA processing. We also created a global reference map to understand NC dynamics under stresses and how disease-related mutations differentially affect NC interactomes. Overall, our work provides a proximal proteome-based atlas for human NCs, substantially advancing our spatiotemporal understanding of nuclear biological events.</p>

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Proximal proteomics reveals a landscape of human nuclear condensates

  • 期刊论文

  • 发表日期：

    2025年11月28日

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  • Ruofei Li,
  • Yingying Li,
  • Su Wu,
  • Zhifen Zhou,
  • Xinyu Hou,
  • Ping Yang,
  • Jun Zhu,
  • Ying Xia,
  • Wenchao Wu,
  • Ran Feng,
  • Qiuyuan Gao,
  • Kunling Huang,
  • Yi Liu,
  • Jianfei Zheng,
  • Xiaoqin Zhong,
  • Hui Huang,
  • Cheng Chang,
  • Wenbin Ma,
  • Zhou Songyang,
  • Feng Liu

摘要

Nuclear condensates (NCs) are membraneless organelles that enable spatial and functional compartmentalization in the nucleus. Yet, the components and functional co-organization of NCs have been poorly studied. Here, we used PhastID to explore the proximal interactome of 18 NCs in HeLa cells. Our data revealed the organizational flow of gene control among these NCs. Crucially, we developed an algorithm to dissect the intricate internal relations of NCs. This algorithm led to key discoveries: the identification of an uncharacterized BUD13 condensate, and the recognition of specific co-organizations between nuclear gems and Cajal bodies for telomerase maturation, and between nuclear gems and histone locus bodies for histone gene pre-mRNA processing. We also created a global reference map to understand NC dynamics under stresses and how disease-related mutations differentially affect NC interactomes. Overall, our work provides a proximal proteome-based atlas for human NCs, substantially advancing our spatiotemporal understanding of nuclear biological events.