Treacle’s ability to form liquid-like phase condensates is essential for nucleolar fibrillar center assembly, efficient rRNA transcription and processing, and rRNA gene repair
We investigated the role of the nucleolar protein Treacle in organizing and regulating the nucleolus in human cells. Our results support Treacle’s ability to form liquid-like phase condensates through electrostatic interactions among molecules. The formation of these biomolecular condensates is cruc...
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eLife Sciences Publications Ltd
2025-04-01
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| Online Access: | https://elifesciences.org/articles/96722 |
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| author | Artem K Velichko Nadezhda V Petrova Dmitry A Deriglazov Anastasia P Kovina Artem V Luzhin Eugene P Kazakov Igor I Kireev Sergey Razin Omar L Kantidze |
| author_facet | Artem K Velichko Nadezhda V Petrova Dmitry A Deriglazov Anastasia P Kovina Artem V Luzhin Eugene P Kazakov Igor I Kireev Sergey Razin Omar L Kantidze |
| author_sort | Artem K Velichko |
| collection | DOAJ |
| description | We investigated the role of the nucleolar protein Treacle in organizing and regulating the nucleolus in human cells. Our results support Treacle’s ability to form liquid-like 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 and ensuring high levels of ribosomal RNA (rRNA) gene transcription and accurate rRNA processing. Both the central and C-terminal domains of Treacle are required to form liquid-like condensates. The initiation of phase separation is attributed to the C-terminal domain. The central domain is characterized by repeated stretches of alternatively charged amino acid residues and is vital for condensate stability. Overexpression of mutant forms of Treacle that cannot form liquid-like phase condensates compromises the assembly of fibrillar centers, suppressing rRNA gene transcription and disrupting rRNA processing. These mutant forms also fail to recruit DNA topoisomerase II binding protein 1 (TOPBP1), suppressing the DNA damage response in the nucleolus. |
| format | Article |
| id | doaj-art-e49768d057144f149ac9b9bd1df06e89 |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-e49768d057144f149ac9b9bd1df06e892025-08-20T02:12:03ZengeLife Sciences Publications LtdeLife2050-084X2025-04-011310.7554/eLife.96722Treacle’s ability to form liquid-like phase condensates is essential for nucleolar fibrillar center assembly, efficient rRNA transcription and processing, and rRNA gene repairArtem K Velichko0https://orcid.org/0009-0006-3105-1988Nadezhda V Petrova1Dmitry A Deriglazov2Anastasia P Kovina3Artem V Luzhin4Eugene P Kazakov5Igor I Kireev6Sergey Razin7Omar L Kantidze8https://orcid.org/0000-0002-7507-7307Department of Cellular Genomics, Institute of Gene Biology RAS, Moscow, Russian Federation; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology RAS, Moscow, Russian Federation; Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russian FederationDepartment of Cellular Genomics, Institute of Gene Biology RAS, Moscow, Russian FederationDepartment of Cellular Genomics, Institute of Gene Biology RAS, Moscow, Russian FederationDepartment of Cellular Genomics, Institute of Gene Biology RAS, Moscow, Russian FederationDepartment of Cellular Genomics, Institute of Gene Biology RAS, Moscow, Russian Federation; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology RAS, Moscow, Russian FederationA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian FederationA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian FederationDepartment of Cellular Genomics, Institute of Gene Biology RAS, Moscow, Russian Federation; Biological Faculty, Lomonosov Moscow State University, Moscow, Russian FederationDepartment of Cellular Genomics, Institute of Gene Biology RAS, Moscow, Russian FederationWe investigated the role of the nucleolar protein Treacle in organizing and regulating the nucleolus in human cells. Our results support Treacle’s ability to form liquid-like 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 and ensuring high levels of ribosomal RNA (rRNA) gene transcription and accurate rRNA processing. Both the central and C-terminal domains of Treacle are required to form liquid-like condensates. The initiation of phase separation is attributed to the C-terminal domain. The central domain is characterized by repeated stretches of alternatively charged amino acid residues and is vital for condensate stability. Overexpression of mutant forms of Treacle that cannot form liquid-like phase condensates compromises the assembly of fibrillar centers, suppressing rRNA gene transcription and disrupting rRNA processing. These mutant forms also fail to recruit DNA topoisomerase II binding protein 1 (TOPBP1), suppressing the DNA damage response in the nucleolus.https://elifesciences.org/articles/96722HeLanucleolusfibrillar centersTreaclecondensationphase separation |
| spellingShingle | Artem K Velichko Nadezhda V Petrova Dmitry A Deriglazov Anastasia P Kovina Artem V Luzhin Eugene P Kazakov Igor I Kireev Sergey Razin Omar L Kantidze Treacle’s ability to form liquid-like phase condensates is essential for nucleolar fibrillar center assembly, efficient rRNA transcription and processing, and rRNA gene repair eLife HeLa nucleolus fibrillar centers Treacle condensation phase separation |
| title | Treacle’s ability to form liquid-like phase condensates is essential for nucleolar fibrillar center assembly, efficient rRNA transcription and processing, and rRNA gene repair |
| title_full | Treacle’s ability to form liquid-like phase condensates is essential for nucleolar fibrillar center assembly, efficient rRNA transcription and processing, and rRNA gene repair |
| title_fullStr | Treacle’s ability to form liquid-like phase condensates is essential for nucleolar fibrillar center assembly, efficient rRNA transcription and processing, and rRNA gene repair |
| title_full_unstemmed | Treacle’s ability to form liquid-like phase condensates is essential for nucleolar fibrillar center assembly, efficient rRNA transcription and processing, and rRNA gene repair |
| title_short | Treacle’s ability to form liquid-like phase condensates is essential for nucleolar fibrillar center assembly, efficient rRNA transcription and processing, and rRNA gene repair |
| title_sort | treacle s ability to form liquid like phase condensates is essential for nucleolar fibrillar center assembly efficient rrna transcription and processing and rrna gene repair |
| topic | HeLa nucleolus fibrillar centers Treacle condensation phase separation |
| url | https://elifesciences.org/articles/96722 |
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