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

Perez-Schindler, Joaquin; Kohl, Bastian; Schneider-Heieck, Konstantin; Leuchtmann, Aurel B.; Henriquez-Olguin, Carlos; Adak, Volkan; Maier, Geraldine; Delezie, Julien; Sakoparnig, Thomas; Vargas-Fernandez, Elyzabeth; Karrer-Cardel, Bettina; Ritz, Danilo; Schmidt, Alexander; Hondele, Maria; Jensen, Thomas E.; et. al.

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 gamma coactivator 1 alpha (PGC-1 alpha) 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-1 alpha to bind RNAs and assemble multiprotein complexes including proteins that control gene transcription and RNA processing. These interactions are important for PGC-1 alpha 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 PGC1 alpha regulates complex transcriptional networks. These findings provide a broad conceptual framework for context-dependent transcriptional control of phenotypic adaptations in metabolically active tissues.

Más información

Título según WOS: ID WOS:000705136000027 Not found in local WOS DB
Título de la Revista: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volumen: 118
Número: 36
Editorial: NATL ACAD SCIENCES
Fecha de publicación: 2021
DOI:

10.1073/pnas.2105951118

Notas: ISI