RNA-bound PGC-1α controls gene expression in liquid-like nuclear condensates
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RNA-bound PGC-1α controls gene expression in liquid-like nuclear condensates. / Pérez-Schindler, Joaquín; Kohl, Bastian; Schneider-Heieck, Konstantin; Leuchtmann, Aurel B; Henríquez-Olguín, Carlos; Adak, Volkan; Maier, Geraldine; Delezie, Julien; Sakoparnig, Thomas; Vargas-Fernández, Elyzabeth; Karrer-Cardel, Bettina; Ritz, Danilo; Schmidt, Alexander; Hondele, Maria; Jensen, Thomas Elbenhardt; Hiller, Sebastian; Handschin, Christoph.
I: Proceedings of the National Academy of Sciences of the United States of America, Bind 118, Nr. 36, e2105951118, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 278486209