RNA scaffolds the Golgi ribbon by forming condensates with GM130

Nat Cell Biol. 2024 Jul;26(7):1139-1153. doi: 10.1038/s41556-024-01447-2. Epub 2024 Jul 11.

Abstract

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.

MeSH terms

  • Animals
  • Autoantigens* / chemistry
  • Autoantigens* / genetics
  • Autoantigens* / metabolism
  • Biomolecular Condensates / metabolism
  • Golgi Apparatus* / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Intracellular Membranes / metabolism
  • Membrane Proteins* / chemistry
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Protein Binding
  • RNA* / genetics
  • RNA* / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism

Substances

  • Golgin subfamily A member 2
  • Autoantigens
  • Membrane Proteins
  • RNA
  • RNA-Binding Proteins