RNA-bound PGC-1α Controls Gene Expression in Liquid-Like Nuclear Condensates

Significance The function of tissues is controlled by complex biological processes, in which transcriptional mechanisms play a fundamental role. The transcriptional coactivator PGC-1α is a prototypical regulator of adaptive responses evoked by environmental and internal cues (e.g. exercise-adaptation in skeletal muscle). Here, we found that PGC-1α-RNA–binding is central to assemble multiprotein complexes controlling gene transcription. Interestingly, PGC-1α-RNA–binding also regulates chromatin recruitment in transcriptionally active liquid-like nuclear condensates. Collectively, our findings unravel mechanistic insights into the regulation of complex transcriptional networks by PGC-1α, which we demonstrate to be essential to enhance the expression of key genes controlling skeletal muscle oxidative metabolism.