加州大学Gary H. Karpen团队的一项最新研究显示，核仁和异染色质凝聚物之间的层次相互作用是由双亲和蛋白介导的。2025年11月24日出版的《自然—细胞生物学》杂志发表了这项成果。

在此，该课题组对果蝇胚胎发生过程中的高分辨率实时成像进行了研究，并揭示了PCH -核仁关联的从头建立是高度动态的，因为PCH从沿核边缘延伸到核仁周围。通过去除核糖体RNA基因来消除核糖体破坏这一过程，导管化增加PCH压实，随后其重组为环状结构。

此外，在缺乏核糖体RNA基因的胚胎中，核仁蛋白被重新分配到新的体或“新凝聚体”中，包括在PCH环状孔中富集。将这些体内观察结果与基于多相润湿理论的分子动力学模拟相结合，揭示了核仁- PCH结合可以通过PCH、核仁和具有双重亲和力的蛋白之间的相互作用强度等级来调节。该研究组通过鉴定一种名为Pitchoune的DEAD-box RNA解旋酶来验证这一模型，并表明其对核仁或PCH成分的亲和力的调节改变了核仁- PCH的组织。总之，这项研究揭示了在动物发育过程中建立核仁- PCH关联的动态程序，并展示了相互作用等级和双亲和分子连接物如何共同组织组成不同的凝聚物。

据悉，核仁被周中心异染色质（PCH）包围，反映了真核生物细胞核中两种最大的生物分子凝聚体之间的保守空间联系。核仁是核糖体合成的位点，而富含重复序列的PCH对于染色体分离、基因组稳定和转录沉默至关重要，但它们共同组装的机制尚不清楚。

附：英文原文

Title: Hierarchical interactions between nucleolar and heterochromatin condensates are mediated by a dual-affinity protein

Author: Rajshekar, Srivarsha, Adame-Arana, Omar, Bajpai, Gaurav, Colmenares, Serafin U., Papoi, Hannah, Brennan, Lucy D., Tsukamoto, Shingo, Safran, Samuel, Karpen, Gary H.

Issue&Volume: 2025-11-24

Abstract: Nucleoli are surrounded by pericentromeric heterochromatin (PCH), reflecting a conserved spatial association between the two largest biomolecular condensates in eukaryotic nuclei. Nucleoli are the sites of ribosome synthesis, whereas the repeat-rich PCH is essential for chromosome segregation, genome stability and transcriptional silencing, yet the mechanisms for their co-assembly are unclear. Here we use high-resolution live imaging during Drosophila embryogenesis and reveal that de novo establishment of PCH–nucleolar associations is highly dynamic, as PCH transitions from extending along the nuclear edge to surrounding the nucleolus. Elimination of the nucleolus by removing the ribosomal RNA genes disrupted this process causing increased PCH compaction, followed by its reorganization into a toroidal structure. Furthermore, in embryos lacking ribosomal RNA genes, nucleolar proteins were redistributed into new bodies or ‘neocondensates’, including enrichment in the PCH toroidal hole. Combining these in vivo observations with molecular dynamics simulations based on multiphase wetting theory revealed that nucleolar–PCH associations can be mediated by a hierarchy of interaction strengths between PCH, nucleoli and proteins with dual affinities for both compartments. We validate this model by identifying such a protein, a DEAD-box RNA helicase called Pitchoune, and show that modulation of its affinity for either nucleolar or PCH components alters nucleolar–PCH organization. Together, this study unveils a dynamic programme for establishing nucleolar–PCH associations during animal development and demonstrates how interaction hierarchies and dual-affinity molecular linkers co-organize compositionally distinct condensates.

DOI: 10.1038/s41556-025-01806-7

Source: https://www.nature.com/articles/s41556-025-01806-7