(MEMPHIS, Tenn. – July 15, 2026) 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 sub-compartments containing ribosome building blocks and assembly proteins spontaneously form to finish the final steps of ribosome assembly. This unearths 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 Richard Kriwacki , PhD, St. Jude Department of Structural Biology , showed that sub-compartments 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 sub-compartments before being engaged by the chaperone protein, NPM1, before their release into the surrounding nucleoplasm when 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 , PhD, Department of Structural Biology.
The researchers found that the interactions between the ribosome building blocks and SURF6 caused them to separate from their surroundings, like oil separating from water, forming isolated sub-compartments or “droplets” within the granular component. “Based on these results, we hypothesized that these sub-compartments 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 sub-compartments help ribosome assembly by preventing NPM1 from associating with the ribosome building blocks until they are assembled. Only when the interactions in the sub-compartments 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 sub-compartments, as well as many other liquid-like cellular compartments, referred to as biomolecular condensates. While the nucleolus was one of the first cellular organelles to be identified as forming through phase separation, this display of “droplets within droplets” demonstrates unprecedented levels of organization present that were 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 uncover future therapeutic avenues.
“Previous work demonstrated that distinct compartments can co-exist within the nucleolus due to physical property differences,” said Ferrolino. “Here, we probed even smaller sub-spaces behind ribosome production. Resolving the granular component at such high resolution and seeing sub-compartments is something really special.”
Authors and funding
The study’s co-first author is Priyanka Dogra, St. Jude. The study’s other authors are Suparna Khatun, Qi Miao, Michele Tolbert, Aaron Pitre, Shondra Pruett-Miller, Swarnendu Tripathi, David Baggett, Jaison John, George Campbell, Katelyn Jackson, Richa Bajpai, Toler Freyaldenhoven, Eric Gibbs and Cheon-Gil Park, St. Jude.
The study was supported by the National Institutes of Health (R35GM131891 and R01GM115634), the National Cancer Institute (P30 CA021765) and the American Lebanese Syrian Associated Charities (ALSAC), the fundraising and awareness organization of St. Jude.
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St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital is leading the way the world understands, treats, and cures childhood catastrophic diseases. From cancer to life-threatening blood disorders, neurological conditions, and infectious diseases, St. Jude is dedicated to advancing cures and means of prevention through groundbreaking research and compassionate care. Through global collaborations and innovative science, St. Jude is working to ensure that every child, everywhere, has the best chance at a healthy future. To learn more, visit stjude.org , read St. Jude Progress, a digital magazine , and follow St. Jude on social media at @stjuderesearch .
Molecular Cell
Experimental study
Cells
Granular component sub-phases direct ribosome biogenesis in the nucleolus
15-Jul-2026