Pérez-Schindler, Joaquín and Kohl, Bastian and Schneider-Heieck, Konstantin and Leuchtmann, Aurel B. and Henríquez-Olguín, Carlos and Adak, Volkan and Maier, Geraldine and Delezie, Julien and Sakoparnig, Thomas and Vargas-Fernández, Elyzabeth and Karrer-Cardel, Bettina and Ritz, Danilo and Schmidt, Alexander and Hondele, Maria and Jensen, Thomas E. and Hiller, Sebastian and Handschin, Christoph. (2021) RNA-bound PGC-1α controls gene expression in liquid-like nuclear condensates. Proceedings of the National Academy of Sciences of the United States of America, 118 (36). e2105951118.
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Official URL: https://edoc.unibas.ch/84574/
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Abstract
Plasticity of cells, tissues, and organs is controlled by the coordinated transcription of biological programs. However, the mechanisms orchestrating such context-specific transcriptional networks mediated by the dynamic interplay of transcription factors and coregulators are poorly understood. The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a prototypical master regulator of adaptive transcription in various cell types. We now uncovered a central function of the C-terminal domain of PGC-1α to bind RNAs and assemble multiprotein complexes including proteins that control gene transcription and RNA processing. These interactions are important for PGC-1α recruitment to chromatin in transcriptionally active liquid-like nuclear condensates. Notably, such a compartmentalization of active transcription mediated by liquid-liquid phase separation was observed in mouse and human skeletal muscle, revealing a mechanism by which PGC-1α regulates complex transcriptional networks. These findings provide a broad conceptual framework for context-dependent transcriptional control of phenotypic adaptations in metabolically active tissues.
Faculties and Departments: | 03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin) 05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin) 05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Proteomics (Schmidt) 05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Hiller) |
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UniBasel Contributors: | Handschin, Christoph and Hiller, Sebastian and Schmidt, Alexander |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | National Academy of Sciences |
ISSN: | 0027-8424 |
e-ISSN: | 1091-6490 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Language: | English |
Identification Number: |
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edoc DOI: | |
Last Modified: | 08 Dec 2022 10:08 |
Deposited On: | 06 Oct 2021 08:23 |
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