Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nat Cell Biol. 2024 Jul;26(7):1139-1153. doi: 10.1038/s41556-024-01447-2. Epub 2024 Jul 11.
The mammalian Golgi is composed of stacks that are laterally connected into a continuous ribbon-like structure. The integrity and function of the ribbon is disrupted under stress conditions, but the molecular mechanisms remain unclear. Here we show that the ribbon is maintained by biomolecular condensates of RNA and the Golgi matrix protein GM130 (GOLGA2). We identify GM130 as a membrane-bound RNA-binding protein, which directly recruits RNA and associated RNA-binding proteins to the Golgi membrane. Acute degradation of RNA or GM130 in cells disrupts the ribbon. Under stress conditions, RNA dissociates from GM130 and the ribbon is disjointed, but after the cells recover from stress the ribbon is restored. When overexpressed in cells, GM130 forms RNA-dependent liquid-like condensates. GM130 contains an intrinsically disordered domain at its amino terminus, which binds RNA to induce liquid-liquid phase separation. These co-condensates are sufficient to link purified Golgi membranes, reconstructing lateral linking of stacks into a ribbon-like structure. Together, these studies show that RNA acts as a structural biopolymer that together with GM130 maintains the integrity of the Golgi ribbon.
哺乳动物高尔基体由堆叠的膜层组成，这些膜层侧向连接形成连续的带状结构。在应激条件下，带状结构的完整性和功能被破坏，但分子机制尚不清楚。在这里，我们发现带状结构是由 RNA 和高尔基基质蛋白 GM130（GOLGA2）组成的生物分子凝聚物维持的。我们确定 GM130 是一种膜结合的 RNA 结合蛋白，它直接将 RNA 和相关的 RNA 结合蛋白招募到高尔基膜上。细胞中 RNA 和 GM130 的急性降解会破坏带状结构。在应激条件下，RNA 从 GM130 上解离，带状结构被打断，但细胞从应激中恢复后，带状结构会被重建。当在细胞中过表达时，GM130 会形成依赖 RNA 的液态凝聚物。GM130 在其氨基末端含有一个固有无序的结构域，该结构域可以结合 RNA 以诱导液-液相分离。这些共凝聚物足以连接纯化的高尔基膜，将膜层的侧向连接重建为带状结构。总之，这些研究表明，RNA 作为一种结构生物聚合物，与 GM130 一起维持着高尔基体带状结构的完整性。
