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PLoS Biol 2023 Nov 01;2111:e3002378. doi: 10.1371/journal.pbio.3002378.
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Intrinsically disordered regions are not sufficient to direct the compartmental localization of nucleolar proteins in the nucleus.

Lavering ED , Gandhamaneni M , Weeks DL .

The nucleolus is a non-membrane bound organelle central to ribosome biogenesis. The nucleolus contains a mix of proteins and RNA and has 3 known nucleolar compartments: the fibrillar center (FC), the dense fibrillar component (DFC), and the granular component (GC). The spatial organization of the nucleolus is influenced by the phase separation properties of nucleolar proteins, the presence of RNA, protein modification, and cellular activity. Many nucleolar proteins appear to concentrate within the borders of the compartments. We investigated whether the intrinsically disordered regions from several proteins provided the information needed to establish specific compartment localization using Xenopus laevis oocytes. For the proteins we tested, the disordered regions were not sufficient to direct specific domain localization and appear dispensable with respect to compartmentalization. Among the proteins that colocalize to the DFC are the quartet that comprise the box H/ACA pseudouridylation complex. In contrast to the insufficiency of IDRs to direct compartment localization, we found that the DFC accumulation of 2 box H/ACA proteins, Gar1 and Nhp2, was disrupted by mutations that were previously shown to reduce their ability to join the box H/ACA complex. Using a nanobody to introduce novel binding to a different DFC localized protein, we restored the localization of the mutated forms of Gar1 and Nhp2.

PubMed ID: 37943867
PMC ID: PMC10662738
Article link: PLoS Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: bop1 dkc1 fbl gar1 gtpbp4 ncl nhp2 nop56 npm1 npm3 pak1ip1 pes1 rpl12
GO keywords: fibrillar center [+]

Article Images: [+] show captions
References [+] :
Alberti, Considerations and Challenges in Studying Liquid-Liquid Phase Separation and Biomolecular Condensates. 2019, Pubmed