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

Research output: Contribution to journalJournal articlepeer-review

  • 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.

Original languageEnglish
Article numbere2105951118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number36
Number of pages11
ISSN0027-8424
DOIs
Publication statusPublished - 2021

    Research areas

  • Faculty of Science - Gene transcription, Transcriptional coactivator, Chromatin, Liquid-liquid phase separation, RNA-binding protein

ID: 278486209