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Biology subjects

Maier, G.

Publications and source records attributed to Maier, G..

2 recordsLinked to original sources

Transcriptomic, proteomic and phosphoproteomic underpinnings of daily exercise performance and Zeitgeber activity of endurance training

Timed physical activity might potentiate the health benefits of training. The underlying signaling events triggered by exercise at different times of the day are, however, poorly understood. Here, we found that time-dependent variations in maximal treadmill exercise capacity of naive mice were associated with energy stores, mostly hepatic glycogen levels. Importantly, running at different times of the day resulted in a vastly different activation of signaling pathways, e.g., related to stress response, vesicular trafficking, repair, and regeneration. Second, voluntary wheel running at the opposite phase of the dark, feeding period surprisingly revealed minimal Zeitgeber (i.e., synchronizing) activity of training. This integrated study provides important insights into the circadian regulation of endurance performance and the control of the circadian clock by exercise. These results are of high importance to understand circadian aspects of training design in athletes and the application of chrono-exercise-based interventions in patients. HighlightsO_LIMaximal endurance performance is greater in the early morning C_LIO_LITimed exercise differentially alters the muscle transcriptome and (phospho)-proteome C_LIO_LIMorning exercise triggers energy provisioning and tissue regeneration C_LIO_LIEvening exercise activates stress-related and catabolic pathways C_LIO_LITraining exerts poor Zeitgeber activity on the muscle and liver clocks C_LI

physiology

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

The peroxisome-proliferator-activated receptor-{gamma} coactivator-1 (PGC-1) integrates environmental cues by controlling complex transcriptional networks in various metabolically active tissues. However, it is unclear how a transcriptional coregulator coordinates dynamic biological programs in response to multifaceted stimuli such as endurance training or fasting. Here, we discovered a central function of the poorly understood C-terminal domain (CTD) of PGC-1 to bind RNAs and assemble multi-protein complexes. Surprisingly, in addition to controlling the coupling of transcription and processing of target genes, RNA binding is indispensable for the recruitment of PGC-1 to chromatin into liquid-like nuclear condensates, which compartmentalize and regulate active transcription. These results demonstrate a hitherto unsuspected molecular mechanism by which complexity in the regulation of large transcriptional networks by PGC-1 is achieved. These findings are not only essential for the basic understanding of transcriptional coregulator-driven control of biological programs, but will also help to devise new strategies to modulate these processes in pathological contexts in which PGC-1 function is dysregulated, such as type 2 diabetes, cardiovascular diseases or skeletal muscle wasting.

molecular biology