Transcriptome-wide analysis of PGC-1α–binding RNAs identifies genes linked to glucagon metabolic action

Significance Glucagon action in liver is a central response to fasting and type 2 diabetes. Glucagon action has been delineated through regulatory mechanisms involving signaling, transcription factor/coactivator-based gluconeogenic gene expression, and metabolic enzyme activity. Understanding the molecular mechanisms whereby glucagon controls energy metabolism will define new strategies and potential therapies to treat metabolic diseases. Here, we have identified a regulatory mechanism whereby PGC-1α, a known transcriptional regulator of glucagon action, binds RNAs linked to glucose energy metabolism. PGC-1α represents a class of RNA-binding proteins that act as a transcriptional coactivator through transcription factor binding, but also binds to RNA sequences to control specific mRNA transcripts encoding for metabolic and bioenergetic genes.