Affiliations
- Artem K. Velichko, Department of Cellular Genomics, Institute of Gene Biology RAS, Moscow, Russia.
- Anastasia P. Kovina, Department of Cellular Genomics, Institute of Gene Biology RAS, Moscow, Russia.
- Artem V. Luzhin, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology RAS, Moscow, Russia.
- Nadezhda V. Petrova, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology RAS, Moscow, Russia.
- Dmitry A. Deriglazov, Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.
- Eugene P. Kazakov, Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.
- Igor I. Kireev, Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.
- Sergey V. Razin, Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.
- Omar L. Kantidze, Department of Cellular Genomics, Institute of Gene Biology RAS, Moscow, Russia; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology RAS, Moscow, Russia; Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.
Abstract
We investigated the role of the nucleolar protein Treacle in organizing and regulating the nucleolus in human cells. Our results support Treacle’s capacity to form liquid-phase condensates through electrostatic interactions among molecules. The formation of these biomolecular condensates is crucial for segregating nucleolar fibrillar centers from the dense fibrillar component, as well as ensuring high levels of rRNA gene transcription and accurate pre-rRNA processing. The presence of both the central and C-terminal domains of Treacle is necessary for the creation of liquid-phase condensates. Initiation of phase separation is attributed to the C-terminal domain, while the central domain, characterized by repeated stretches of alternatively charged amino-acid residues, is vital for maintaining the condensate’s liquid state.
When mutant forms of Treacle, incapable of forming liquid-phase condensates, are overexpressed in cells, it compromises the establishment of fibrillar centers, leading to the suppression of rRNA transcription and disruption of its processing. Additionally, these mutant forms fail to recruit TOPBP1, resulting in the suppression of the DNA damage response in the nucleolus.
