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The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function.
Mihaylov, Simeon R; Castelli, Lydia M; Lin, Ya-Hui; Gül, Aytac; Soni, Nikita; Hastings, Christopher; Flynn, Helen R; Paun, Oana; Dickman, Mark J; Snijders, Ambrosius P; Goldstone, Robert; Bandmann, Oliver; Shelkovnikova, Tatyana A; Mortiboys, Heather; Ultanir, Sila K; Hautbergue, Guillaume M.
Afiliação
  • Mihaylov SR; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK.
  • Castelli LM; Kinases and Brain Development Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
  • Lin YH; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK.
  • Gül A; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK.
  • Soni N; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK.
  • Hastings C; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK.
  • Flynn HR; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK.
  • Paun O; Proteomics Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
  • Dickman MJ; Neural Stem Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
  • Snijders AP; Department of Chemical and Biological Engineering, Sir Robert Hadfield Building, University of Sheffield, Mappin Street, Sheffield, S1 3JD, UK.
  • Goldstone R; Neuroscience Institute, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK.
  • Bandmann O; Proteomics Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
  • Shelkovnikova TA; Life Science Mass Spectrometry, Bruker Daltonics, Banner Lane, Coventry, CV4 9GH, UK.
  • Mortiboys H; Bioinformatics and Biostatistics Science and Technology Platform, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
  • Ultanir SK; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK.
  • Hautbergue GM; Neuroscience Institute, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK.
Nat Commun ; 14(1): 5496, 2023 09 07.
Article em En | MEDLINE | ID: mdl-37679383
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA / Transporte de RNA Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2023 Tipo de documento: Article País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA / Transporte de RNA Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2023 Tipo de documento: Article País de publicação: Reino Unido