The coilin N-terminus mediates multivalent interactions between coilin and Nopp140 to form and maintain Cajal bodies.

Autor: Courchaine E; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA., Gelles-Watnick S; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA., Machyna M; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA., Straube K; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA., Sauyet S; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA., Enright J; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA., Neugebauer KM; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA. karla.neugebauer@yale.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Oct 12; Vol. 13 (1), pp. 6005. Date of Electronic Publication: 2022 Oct 12.
DOI: 10.1038/s41467-022-33434-2
Abstrakt: Cajal bodies (CBs) are ubiquitous nuclear membraneless organelles (MLOs) that concentrate and promote efficient biogenesis of snRNA-protein complexes involved in splicing (snRNPs). Depletion of the CB scaffolding protein coilin disperses snRNPs, making CBs a model system for studying the structure and function of MLOs. Although it is assumed that CBs form through condensation, the biomolecular interactions responsible remain elusive. Here, we discover the unexpected capacity of coilin's N-terminal domain (NTD) to form extensive fibrils in the cytoplasm and discrete nuclear puncta in vivo. Single amino acid mutational analysis reveals distinct molecular interactions between coilin NTD proteins to form fibrils and additional NTD interactions with the nuclear Nopp140 protein to form puncta. We provide evidence that Nopp140 has condensation capacity and is required for CB assembly. From these observations, we propose a model in which coilin NTD-NTD mediated assemblies make multivalent contacts with Nopp140 to achieve biomolecular condensation in the nucleus.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz: