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

Author

Listed:
  • Simeon R. Mihaylov

    (University of Sheffield
    The Francis Crick Institute)

  • Lydia M. Castelli

    (University of Sheffield)

  • Ya-Hui Lin

    (University of Sheffield)

  • Aytac Gül

    (University of Sheffield)

  • Nikita Soni

    (University of Sheffield)

  • Christopher Hastings

    (University of Sheffield)

  • Helen R. Flynn

    (The Francis Crick Institute)

  • Oana Păun

    (The Francis Crick Institute)

  • Mark J. Dickman

    (University of Sheffield
    University of Sheffield, Western Bank)

  • Ambrosius P. Snijders

    (The Francis Crick Institute
    Bruker Daltonics)

  • Robert Goldstone

    (The Francis Crick Institute)

  • Oliver Bandmann

    (University of Sheffield
    University of Sheffield, Western Bank
    University of Sheffield, Western Bank)

  • Tatyana A. Shelkovnikova

    (University of Sheffield
    University of Sheffield, Western Bank)

  • Heather Mortiboys

    (University of Sheffield
    University of Sheffield, Western Bank
    University of Sheffield, Western Bank)

  • Sila K. Ultanir

    (The Francis Crick Institute)

  • Guillaume M. Hautbergue

    (University of Sheffield
    University of Sheffield, Western Bank
    University of Sheffield, Western Bank)

Abstract

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.

Suggested Citation

  • Simeon R. Mihaylov & Lydia M. Castelli & Ya-Hui Lin & Aytac Gül & Nikita Soni & Christopher Hastings & Helen R. Flynn & Oana Păun & Mark J. Dickman & Ambrosius P. Snijders & Robert Goldstone & Oliver, 2023. "The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41304-8
    DOI: 10.1038/s41467-023-41304-8
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    References listed on IDEAS

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    1. Stephan Herzig & Fanxin Long & Ulupi S. Jhala & Susan Hedrick & Rebecca Quinn & Anton Bauer & Dorothea Rudolph & Gunther Schutz & Cliff Yoon & Pere Puigserver & Bruce Spiegelman & Marc Montminy, 2001. "Correction: CREB regulates hepatic gluconeogenesis through the coactivator PGC-1," Nature, Nature, vol. 413(6856), pages 652-652, October.
    2. J. Cliff Yoon & Pere Puigserver & Guoxun Chen & Jerry Donovan & Zhidan Wu & James Rhee & Guillaume Adelmant & John Stafford & C. Ronald Kahn & Daryl K. Granner & Christopher B. Newgard & Bruce M. Spie, 2001. "Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1," Nature, Nature, vol. 413(6852), pages 131-138, September.
    3. Koichi Hasegawa & Toru Yasuda & Chinatsu Shiraishi & Kazushiro Fujiwara & Serge Przedborski & Hideki Mochizuki & Kazuaki Yoshikawa, 2016. "Promotion of mitochondrial biogenesis by necdin protects neurons against mitochondrial insults," Nature Communications, Nature, vol. 7(1), pages 1-15, April.
    4. Stephan Herzig & Fanxin Long & Ulupi S. Jhala & Susan Hedrick & Rebecca Quinn & Anton Bauer & Dorothea Rudolph & Gunther Schutz & Cliff Yoon & Pere Puigserver & Bruce Spiegelman & Marc Montminy, 2001. "CREB regulates hepatic gluconeogenesis through the coactivator PGC-1," Nature, Nature, vol. 413(6852), pages 179-183, September.
    5. Nicolas Viphakone & Guillaume M. Hautbergue & Matthew Walsh & Chung-Te Chang & Arthur Holland & Eric G. Folco & Robin Reed & Stuart A. Wilson, 2012. "TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export," Nature Communications, Nature, vol. 3(1), pages 1-14, January.
    6. Joseph T. Rodgers & Carlos Lerin & Wilhelm Haas & Steven P. Gygi & Bruce M. Spiegelman & Pere Puigserver, 2005. "Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1," Nature, Nature, vol. 434(7029), pages 113-118, March.
    7. Guillaume M. Hautbergue & Lydia M. Castelli & Laura Ferraiuolo & Alvaro Sanchez-Martinez & Johnathan Cooper-Knock & Adrian Higginbottom & Ya-Hui Lin & Claudia S. Bauer & Jennifer E. Dodd & Monika A. M, 2017. "SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits," Nature Communications, Nature, vol. 8(1), pages 1-18, December.
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