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RNA-bound PGC-1α controls gene expression in liquid-like nuclear condensates

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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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)
UniBasel Contributors:Handschin, Christoph
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
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Last Modified:06 Oct 2021 08:23
Deposited On:06 Oct 2021 08:23

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