Elucidating structure–function relationships in the mammalian nucleolus

Banani, S. F., Lee, H. O., Hyman, A. A. & Rosen, M. K. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18, 285–298 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mittag, T. & Pappu, R. V. A conceptual framework for understanding phase separation and addressing open questions and challenges. Mol. Cell 82, 2201–2214 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hirose, T., Ninomiya, K., Nakagawa, S. & Yamazaki, T. A guide to membraneless organelles and their various roles in gene regulation. Nat. Rev. Mol. Cell Biol. 24, 288–304 (2022).

Article  PubMed  Google Scholar 

Mao, Y. S., Zhang, B. & Spector, D. L. Biogenesis and function of nuclear bodies. Trends Genet. 27, 295–306 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pappu, R. V., Cohen, S. R., Dar, F., Farag, M. & Kar, M. Phase transitions of associative biomacromolecules. Chem. Rev. 123, 8945–8987 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Villegas, J. A., Heidenreich, M. & Levy, E. D. Molecular and environmental determinants of biomolecular condensate formation. Nat. Chem. Biol. 18, 1319–1329 (2022).

Article  CAS  PubMed  Google Scholar 

Wadsworth, G. M. et al. RNA-driven phase transitions in biomolecular condensates. Mol. Cell 84, 3692–3705 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schwarzacher, H. G. & Wachtler, F. Nucleolus organizer regions and nucleoli. Hum. Genet. 63, 89–99 (1983).

Article  CAS  PubMed  Google Scholar 

Pederson, T. The nucleolus. Cold Spring Harb. Perspect. Biol. https://doi.org/10.1101/cshperspect.a000638 (2011).

King, M. R., Ruff, K. M. & Pappu, R. V. Emergent microenvironments of nucleoli. Nucleus 15, 2319957 (2024).

Article  PubMed  PubMed Central  Google Scholar 

Lafontaine, D. L. J., Riback, J. A., Bascetin, R. & Brangwynne, C. P. The nucleolus as a multiphase liquid condensate. Nat. Rev. Mol. Cell Biol. 22, 165–182 (2021).

Article  CAS  PubMed  Google Scholar 

Stenstrom, L. et al. Mapping the nucleolar proteome reveals a spatiotemporal organization related to intrinsic protein disorder. Mol. Syst. Biol. 16, e9469 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Boisvert, F. M., van Koningsbruggen, S., Navascues, J. & Lamond, A. I. The multifunctional nucleolus. Nat. Rev. Mol. Cell Biol. 8, 574–585 (2007).

Article  CAS  PubMed  Google Scholar 

Lazdins, I. B., Delannoy, M. & Sollner-Webb, B. Analysis of nucleolar transcription and processing domains and pre-rRNA movements by in situ hybridization. Chromosoma 105, 481–495 (1997).

Article  CAS  PubMed  Google Scholar 

Thiry, M. & Lafontaine, D. L. Birth of a nucleolus: the evolution of nucleolar compartments. Trends Cell Biol. 15, 194–199 (2005).

Article  CAS  PubMed  Google Scholar 

Stanek, D. et al. Non-isotopic mapping of ribosomal RNA synthesis and processing in the nucleolus. Chromosoma 110, 460–470 (2001).

Article  CAS  PubMed  Google Scholar 

Yao, R. W. et al. Nascent pre-rRNA sorting via phase separation drives the assembly of dense fibrillar components in the human nucleolus. Mol. Cell 76, 767–783 (2019).

Article  CAS  PubMed  Google Scholar 

Shan, L. et al. Nucleolar URB1 ensures 3′ ETS rRNA removal to prevent exosome surveillance. Nature 615, 526–534 (2023).

Article  CAS  PubMed  Google Scholar 

Dodel, M. et al. TREX reveals proteins that bind to specific RNA regions in living cells. Nat. Methods 21, 423–434 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Olson, M. O., Dundr, M. & Szebeni, A. The nucleolus: an old factory with unexpected capabilities. Trends Cell Biol. 10, 189–196 (2000).

Article  CAS  PubMed  Google Scholar 

Leung, A. K. & Lamond, A. I. The dynamics of the nucleolus. Crit. Rev. Eukaryot. Gene Expr. 13, 39–54 (2003).

Article  CAS  PubMed  Google Scholar 

Riback, J. A. et al. Viscoelasticity and advective flow of RNA underlies nucleolar form and function. Mol. Cell 83, 3095–3107 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Erdmann, P. S. et al. In situ cryo-electron tomography reveals gradient organization of ribosome biogenesis in intact nucleoli. Nat. Commun. 12, 5364 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Riback, J. A. et al. Composition-dependent thermodynamics of intracellular phase separation. Nature 581, 209–214 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Calo, E. et al. Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders. Nature 554, 112–117 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee, T. A. et al. The nucleolus is the site for inflammatory RNA decay during infection. Nat. Commun. 13, 5203 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sirozh, O. et al. Nucleolar stress caused by arginine-rich peptides triggers a ribosomopathy and accelerates aging in mice. Mol. Cell 84, 1527–1540 (2024).

Article  CAS  PubMed  Google Scholar 

Ma, K. et al. Ribosomal RNA regulates chromosome clustering during mitosis. Cell Discov. https://doi.org/10.1038/s41421-022-00400-7 (2022).

Yamamoto, T., Yamazaki, T., Ninomiya, K. & Hirose, T. Nascent ribosomal RNA act as surfactant that suppresses growth of fibrillar centers in nucleolus. Commun. Biol. 6, 1129 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Quinodoz, S. A. et al. Mapping and engineering RNA-driven architecture of the multiphase nucleolus. Nature https://doi.org/10.1038/s41586-025-09207-4 (2025).

Article  PubMed  PubMed Central  Google Scholar 

Xing, Y. H. et al. SLERT regulates DDX21 rings associated with Pol I transcription. Cell 169, 664–678 (2017).

Article  CAS  PubMed  Google Scholar 

Savić, N. et al. lncRNA maturation to initiate heterochromatin formation in the nucleolus is required for exit from pluripotency in ESCs. Cell Stem Cell 15, 720–734 (2014).

Article  PubMed  Google Scholar

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