IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41304-8.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41304-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41304-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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. 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.
    4. 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.
    5. 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.
    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. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yuta Ozaki & Koji Ohashi & Naoya Otaka & Hiroshi Kawanishi & Tomonobu Takikawa & Lixin Fang & Kunihiko Takahara & Minako Tatsumi & Sohta Ishihama & Mikito Takefuji & Katsuhiro Kato & Yuuki Shimizu & Y, 2023. "Myonectin protects against skeletal muscle dysfunction in male mice through activation of AMPK/PGC1α pathway," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Storm N. S. Reid & Joung-Hyun Park & Yunsook Kim & Yi Sub Kwak & Byeong Hwan Jeon, 2020. "In Vitro and In Vivo Effects of Fermented Oyster-Derived Lactate on Exercise Endurance Indicators in Mice," IJERPH, MDPI, vol. 17(23), pages 1-17, November.
    3. Yue Liu & Yue Yang & Chenying Xu & Jianxing Liu & Jiale Chen & Guoqing Li & Bin Huang & Yi Pan & Yanfeng Zhang & Qiong Wei & Stephen J. Pandol & Fangfang Zhang & Ling Li & Liang Jin, 2023. "Circular RNA circGlis3 protects against islet β-cell dysfunction and apoptosis in obesity," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Pengfei Xu & Yingjie Zhang & Xinghao Jiang & Junyan Li & Liying Song & Mir Hasson Khoso & Yunye Liu & Qiang Wu & Guiping Ren & Deshan Li, 2016. "Canine Fibroblast Growth Factor 21 Ameliorates Hyperglycemia Associated with Inhibiting Hepatic Gluconeogenesis and Improving Pancreatic Beta-Cell Survival in Diabetic Mice and Dogs," PLOS ONE, Public Library of Science, vol. 11(5), pages 1-19, May.
    5. Ewa Bielczyk-Maczynska & Meng Zhao & Peter-James H. Zushin & Theresia M. Schnurr & Hyun-Jung Kim & Jiehan Li & Pratima Nallagatla & Panjamaporn Sangwung & Chong Y. Park & Cameron Cornn & Andreas Stahl, 2022. "G protein-coupled receptor 151 regulates glucose metabolism and hepatic gluconeogenesis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Qian Ye & Yi Liu & Guiji Zhang & Haijun Deng & Xiaojun Wang & Lin Tuo & Chang Chen & Xuanming Pan & Kang Wu & Jiangao Fan & Qin Pan & Kai Wang & Ailong Huang & Ni Tang, 2023. "Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    7. Michelle L. Headland & Peter M. Clifton & Jennifer B. Keogh, 2019. "Effects of Weight Loss on FGF-21 in Human Subjects: An Exploratory Study," IJERPH, MDPI, vol. 16(23), pages 1-5, December.
    8. Mirjana Malnar Črnigoj & Urša Čerček & Xiaoke Yin & Manh Tin Ho & Barbka Repic Lampret & Manuela Neumann & Andreas Hermann & Guy Rouleau & Beat Suter & Manuel Mayr & Boris Rogelj, 2023. "Phenylalanine-tRNA aminoacylation is compromised by ALS/FTD-associated C9orf72 C4G2 repeat RNA," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Guanlan Hu & Catriona Ling & Lijun Chi & Mehakpreet K. Thind & Samuel Furse & Albert Koulman & Jonathan R. Swann & Dorothy Lee & Marjolein M. Calon & Celine Bourdon & Christian J. Versloot & Barbara M, 2022. "The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    10. Liang Yang & Junfeng Shen & Chunhua Liu & Zhonghua Kuang & Yong Tang & Zhengjiang Qian & Min Guan & Yongfeng Yang & Yang Zhan & Nan Li & Xiang Li, 2023. "Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Ken-ichi Fujita & Misa Ito & Midori Irie & Kotaro Harada & Naoko Fujiwara & Yuya Ikeda & Hanae Yoshioka & Tomohiro Yamazaki & Masaki Kojima & Bunzo Mikami & Akila Mayeda & Seiji Masuda, 2024. "Structural differences between the closely related RNA helicases, UAP56 and URH49, fashion distinct functional apo-complexes," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    12. Kanwar Abhay Singh & John Soukar & Mohammad Zulkifli & Anna Kersey & Giriraj Lokhande & Sagnika Ghosh & Aparna Murali & Natalie M. Garza & Harman Kaur & Justin N. Keeney & Ramu Banavath & Hatice Ceyla, 2024. "Atomic vacancies of molybdenum disulfide nanoparticles stimulate mitochondrial biogenesis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    13. Liang Chen & Yucong Wang & Jiamei Lin & Zhenxing Song & Qinwei Wang & Wenfang Zhao & Yan Wang & Xiaoyu Xiu & Yuqi Deng & Xiuzhi Li & Qiqi Li & Xiaolin Wang & Jingxin Li & Xu Liu & Kunpeng Liu & Jincon, 2022. "Exportin 4 depletion leads to nuclear accumulation of a subset of circular RNAs," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    14. Amanda M. Gleixner & Brandie Morris Verdone & Charlton G. Otte & Eric N. Anderson & Nandini Ramesh & Olivia R. Shapiro & Jenna R. Gale & Jocelyn C. Mauna & Jacob R. Mann & Katie E. Copley & Elizabeth , 2022. "NUP62 localizes to ALS/FTLD pathological assemblies and contributes to TDP-43 insolubility," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    15. Yoona Kim & Peter Clifton, 2018. "Curcumin, Cardiometabolic Health and Dementia," IJERPH, MDPI, vol. 15(10), pages 1-34, September.
    16. Jae Woo Park & Eun Roh & Gil Myoung Kang & So Young Gil & Hyun Kyong Kim & Chan Hee Lee & Won Hee Jang & Se Eun Park & Sang Yun Moon & Seong Jun Kim & So Yeon Jeong & Chae Beom Park & Hyo Sun Lim & Yu, 2023. "Circulating blood eNAMPT drives the circadian rhythms in locomotor activity and energy expenditure," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41304-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.