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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Joaquín Pérez-Schindler
  • Bastian Kohl
  • Konstantin Schneider-Heieck
  • Aurel B Leuchtmann
  • Henriquez Olguín, Carlos
  • Volkan Adak
  • Geraldine Maier
  • Julien Delezie
  • Thomas Sakoparnig
  • Elyzabeth Vargas-Fernández
  • Bettina Karrer-Cardel
  • Danilo Ritz
  • Alexander Schmidt
  • Maria Hondele
  • Jensen, Thomas Elbenhardt
  • Sebastian Hiller
  • Christoph Handschin

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.

TidsskriftProceedings of the National Academy of Sciences of the United States of America
Udgave nummer36
Antal sider11
StatusUdgivet - 2021

Bibliografisk note

CURIS 2021 NEXS 280

ID: 278486209