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The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function
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The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function
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Journal Article
The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function
2023
Overview
PGC-1α 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-1α directly interacts with RNA and the nuclear RNA export receptor NXF1. Inducible depletion of PGC-1α and expression of RNAi-resistant RS-deleted PGC-1α 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-1α in non-homologous end-joining and nucleocytoplasmic transport. These findings provide new directions to further elucidate the roles of PGC-1α in gene expression, metabolic disorders, aging and neurodegeneration.
PGC-1α is a master regulator activating the transcription of key genes controlling the cell’s energy production. Here the authors show that PGC-1α has a function in the NXF1-dependent nuclear export of mRNAs.
