TY - JOUR

T1 - RNA-bound PGC-1α controls gene expression in liquid-like nuclear condensates

AU - Pérez-Schindler, Joaquín

AU - Kohl, Bastian

AU - Schneider-Heieck, Konstantin

AU - Leuchtmann, Aurel B

AU - Henríquez-Olguín, Carlos

AU - Adak, Volkan

AU - Maier, Geraldine

AU - Delezie, Julien

AU - Sakoparnig, Thomas

AU - Vargas-Fernández, Elyzabeth

AU - Karrer-Cardel, Bettina

AU - Ritz, Danilo

AU - Schmidt, Alexander

AU - Hondele, Maria

AU - Jensen, Thomas Elbenhardt

AU - Hiller, Sebastian

AU - Handschin, Christoph

N1 - CURIS 2021 NEXS 280

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Faculty of Science

KW - Gene transcription

KW - Transcriptional coactivator

KW - Chromatin

KW - Liquid-liquid phase separation

KW - RNA-binding protein

U2 - 10.1073/pnas.2105951118

DO - 10.1073/pnas.2105951118

M3 - Journal article

C2 - 34465622

VL - 118

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 36

M1 - e2105951118

ER -