The master energy homeostasis regulator PGC-1a exhibits an mRNA nuclear export function

PGC-1 & alpha; plays a central role in maintaining mitochondrial and energy metabolism homeostasis, linking external stimuli to transcriptional co-activation of genes involved in adaptive and age-related pathways. The carboxyl-terminus encodes a serine/arginine-rich (RS) region and an RNA recognition motif, however the RNA-processing function(s) were poorly investigated over the past 20 years. Here, we show that the RS domain of human PGC-1 & alpha; directly interacts with RNA and the nuclear RNA export receptor NXF1. Inducible depletion of PGC-1 & alpha; and expression of RNAi-resistant RS-deleted PGC-1 & alpha; further demonstrate that its RNA/NXF1-binding activity is required for the nuclear export of some canonical mitochondrial-related mRNAs and mitochondrial homeostasis. Genome-wide investigations reveal that the nuclear export function is not strictly linked to promoter-binding, identifying in turn novel regulatory targets of PGC-1 & alpha; in non-homologous end-joining and nucleocytoplasmic transport. These findings provide new directions to further elucidate the roles of PGC-1 & alpha; in gene expression, metabolic disorders, aging and neurodegeneration. PGC-1 & alpha; is a master regulator activating the transcription of key genes controlling the cell's energy production. Here the authors show that PGC-1 & alpha; has a function in the NXF1-dependent nuclear export of mRNAs.