Scientists explain how nucleolus sub-compartments drive ribosome assembly
The nucleolus is a liquid-like cellular organelle where protein factories called ribosomes are assembled. Researchers knew of three distinct compartments within the nucleolus, but how these compartments function to drive ribosome assembly was unclear. A study from St. Jude Children's Research Hospital, published today in Molecular Cell, reveals that smaller subcompartments containing ribosome building blocks and assembly proteins spontaneously form to finish the final steps of ribosome assembly. This reveals unprecedented levels of organization behind the process and may offer insight into diseases associated with increased ribosome production, such as cancer.
The study, led by co-corresponding author Richard Kriwacki, Ph.D., showed that subcompartments within the outer region of the nucleolus lock major ribosome building blocks (ribosomal RNA) together with the assembly protein SURF6 until the ribosome is assembled. Assembling ribosomes move through these subcompartments before being engaged by the chaperone protein NPM1 and released into the surrounding nucleoplasm once fully constructed.
SURF6 and ribosome building blocks locked in place
The final steps of ribosome assembly occur in the outermost compartment, or component, of the nucleolus, called the "granular component" for its busy, grainy appearance in electron microscopy. "We were trying to understand how ribosome assembly occurs in this component, which contains hundreds of proteins in a liquid-like environment, and how this environment favors the assembly process," said co-first author Mylene Ferrolino, Ph.D., of the Department of Structural Biology.
The researchers found that interactions between the ribosome building blocks and SURF6 caused them to separate from their surroundings, like oil separating from water, forming isolated subcompartments, or "droplets," within the granular component.
"Based on these results, we hypothesized that these subcompartments contribute to the heterogeneity previously seen under electron microscopy," said Kriwacki. "That hypothesis was supported through super-resolution imaging studies in collaboration with the Cell and Tissue Imaging Center and Center for Bioimage Informatics at St. Jude."
The subcompartments help ribosome assembly by preventing NPM1 from associating with the ribosome building blocks until they are assembled. Only when interactions in the subcompartments weaken is NPM1 allowed to extract the assembled ribosome and move it along its path out of the nucleolus.
The findings highlight the key role of biomolecular phase separation, the driving force behind the formation of the nucleolus and its subcompartments, as well as many other liquid-like cellular compartments referred to as biomolecular condensates. While the nucleolus was one of the first cellular organelles identified as forming through phase separation, this display of "droplets within droplets" demonstrates unprecedented levels of organization that went undetected before this study. Additionally, increased ribosome production is associated with diseases such as cancer, and understanding how these protein factories are built is therefore vital to uncovering future therapeutic avenues.
"Previous work demonstrated that distinct compartments can coexist within the nucleolus due to physical property differences," said Ferrolino. "Here, we probed even smaller subspaces behind ribosome production. Resolving the granular component at such high resolution and seeing subcompartments is something really special."
Publication details
Priyanka Dogra et al, Granular component sub-phases direct ribosome biogenesis in the nucleolus, Molecular Cell (2026). DOI: 10.1016/j.molcel.2026.06.035. www.cell.com/molecular-cell/fu … 1097-2765(26)00424-7
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Citation: Scientists explain how nucleolus sub-compartments drive ribosome assembly (2026, July 15) retrieved 16 July 2026 from https://phys.org/news/2026-07-scientists-nucleolus-compartments-ribosome.html
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