Proteomics

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The master energy homeostasis regulator PGC-1α couples transcriptional co-activation and mRNA nuclear export


ABSTRACT: PGC-1α plays a central role in maintaining the mitochondrial and energy metabolism homeostasis, linking external stimuli to the transcriptional co-activation of genes involved in adaptive and age-related pathways. The carboxyl-terminus encodes a serine/arginine-rich (RS) region and a putative RNA recognition motif, however potential RNA-processing role(s) have remained elusive for the past 20 years. Here, we show that the RS domain of human PGC-1α directly interacts with RNA and the nuclear RNA export factor NXF1. Inducible depletion of endogenous PGC-1α and expression of RNAi-resistant RS-deleted PGC-1α further demonstrate that the RNA-binding activity is required for nuclear export of co-activated transcripts and mitochondrial homeostasis. Moreover, a quantitative proteomics approach confirmed PGC-1α-dependent RNA transport and mitochondrial-related functions, identifying also novel mRNA nuclear export targets in age-related telomere maintenance. Discovering a novel function for a major cellular homeostasis regulator provides new directions to further elucidate the roles of PGC-1α in gene expression, metabolic disorders, ageing and neurodegenerative diseases.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Simeon Mihaylov  

LAB HEAD: Guillaume M Hautbergue

PROVIDER: PXD031189 | Pride | 2023-09-06

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
DNU9921A26RW11-40-576455.raw Raw
DNU9921A26RW12-40-576463.raw Raw
DNU9921A26RW13-40-576464.raw Raw
DNU9921A26RW14-40-576456.raw Raw
DNU9921A26RW15-40-576465.raw Raw
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