近日，美国圣路易斯华盛顿大学Rohit V. Pappu及其课题组发现，大分子凝聚组织核仁亚相来形成pH梯度。这一研究成果于2024年3月18日在线发表在国际学术期刊《细胞》上。

研究人员发现了不同的固有无序区（IDR），包括酸性（D/E）束和由E富集区域穿插的K区，它们是核仁蛋白质的决定性特征。研究表明，核仁蛋白的定位偏好是由其IDR及其所包含的RNA或DNA结合域类型决定的。体外重构和细胞中的研究表明，核仁成分的结合和复合共轭是如何促成核仁组织的。

核仁蛋白质的D/E束有助于降低与核仁RNA在体外形成的共凝聚物的pH值。在细胞中，这会在核仁和核质之间形成pH梯度。相比之下，具有不同大分子组成、电荷分布迥异蛋白质IDR的核仁pH值相当于或高于核质。这些研究结果表明，不同的组成特异性会产生凝聚物的不同理化特性。

据悉，核仁是由共存亚相定义的多组分凝聚体。

附：英文原文

Title: Macromolecular condensation organizes nucleolar sub-phases to set up a pH gradient

Author: Matthew R. King, Kiersten M. Ruff, Andrew Z. Lin, Avnika Pant, Mina Farag, Jared M. Lalmansingh, Tingting Wu, Martin J. Fossat, Wei Ouyang, Matthew D. Lew, Emma Lundberg, Michael D. Vahey, Rohit V. Pappu

Issue&Volume: 2024-03-18

Abstract: Nucleoli are multicomponent condensates defined by coexisting sub-phases. We identified distinct intrinsically disordered regions (IDRs), including acidic (D/E) tracts and K-blocks interspersed by E-rich regions, as defining features of nucleolar proteins. We show that the localization preferences of nucleolar proteins are determined by their IDRs and the types of RNA or DNA binding domains they encompass. In vitro reconstitutions and studies in cells showed how condensation, which combines binding and complex coacervation of nucleolar components, contributes to nucleolar organization. D/E tracts of nucleolar proteins contribute to lowering the pH of co-condensates formed with nucleolar RNAs in vitro. In cells, this sets up a pH gradient between nucleoli and the nucleoplasm. By contrast, juxta-nucleolar bodies, which have different macromolecular compositions, featuring protein IDRs with very different charge profiles, have pH values that are equivalent to or higher than the nucleoplasm. Our findings show that distinct compositional specificities generate distinct physicochemical properties for condensates.

DOI: 10.1016/j.cell.2024.02.029

Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00232-0