IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-35922-5.html
   My bibliography  Save this article

Active mRNA degradation by EXD2 nuclease elicits recovery of transcription after genotoxic stress

Author

Listed:
  • Jérémy Sandoz

    (C.U. Equipe Labellisée Ligue contre le Cancer
    Centre National de la Recherche Scientifique
    Institut National de la Santé et de la Recherche Médicale
    Université de Strasbourg)

  • Max Cigrang

    (C.U. Equipe Labellisée Ligue contre le Cancer
    Centre National de la Recherche Scientifique
    Institut National de la Santé et de la Recherche Médicale
    Université de Strasbourg)

  • Amélie Zachayus

    (C.U. Equipe Labellisée Ligue contre le Cancer
    Centre National de la Recherche Scientifique
    Institut National de la Santé et de la Recherche Médicale
    Université de Strasbourg)

  • Philippe Catez

    (C.U. Equipe Labellisée Ligue contre le Cancer
    Centre National de la Recherche Scientifique
    Institut National de la Santé et de la Recherche Médicale
    Université de Strasbourg)

  • Lise-Marie Donnio

    (Université Claude Bernard Lyon 1)

  • Clèmence Elly

    (C.U. Equipe Labellisée Ligue contre le Cancer
    Centre National de la Recherche Scientifique
    Institut National de la Santé et de la Recherche Médicale
    Université de Strasbourg)

  • Jadwiga Nieminuszczy

    (The Institute of Cancer Research)

  • Pietro Berico

    (C.U. Equipe Labellisée Ligue contre le Cancer
    Centre National de la Recherche Scientifique
    Institut National de la Santé et de la Recherche Médicale
    Université de Strasbourg)

  • Cathy Braun

    (C.U. Equipe Labellisée Ligue contre le Cancer
    Centre National de la Recherche Scientifique
    Institut National de la Santé et de la Recherche Médicale
    Université de Strasbourg)

  • Sergey Alekseev

    (C.U. Equipe Labellisée Ligue contre le Cancer
    Centre National de la Recherche Scientifique
    Institut National de la Santé et de la Recherche Médicale
    Université de Strasbourg)

  • Jean-Marc Egly

    (C.U. Equipe Labellisée Ligue contre le Cancer
    Centre National de la Recherche Scientifique
    Institut National de la Santé et de la Recherche Médicale
    Université de Strasbourg)

  • Wojciech Niedzwiedz

    (The Institute of Cancer Research)

  • Giuseppina Giglia-Mari

    (Université Claude Bernard Lyon 1)

  • Emmanuel Compe

    (C.U. Equipe Labellisée Ligue contre le Cancer
    Centre National de la Recherche Scientifique
    Institut National de la Santé et de la Recherche Médicale
    Université de Strasbourg)

  • Frédéric Coin

    (C.U. Equipe Labellisée Ligue contre le Cancer
    Centre National de la Recherche Scientifique
    Institut National de la Santé et de la Recherche Médicale
    Université de Strasbourg)

Abstract

The transcriptional response to genotoxic stress involves gene expression arrest, followed by recovery of mRNA synthesis (RRS) after DNA repair. We find that the lack of the EXD2 nuclease impairs RRS and decreases cell survival after UV irradiation, without affecting DNA repair. Overexpression of wild-type, but not nuclease-dead EXD2, restores RRS and cell survival. We observe that UV irradiation triggers the relocation of EXD2 from mitochondria to the nucleus. There, EXD2 is recruited to chromatin where it transiently interacts with RNA Polymerase II (RNAPII) to promote the degradation of nascent mRNAs synthesized at the time of genotoxic attack. Reconstitution of the EXD2-RNAPII partnership on a transcribed DNA template in vitro shows that EXD2 primarily interacts with an elongation-blocked RNAPII and efficiently digests mRNA. Overall, our data highlight a crucial step in the transcriptional response to genotoxic attack in which EXD2 interacts with elongation-stalled RNAPII on chromatin to potentially degrade the associated nascent mRNA, allowing transcription restart after DNA repair.

Suggested Citation

  • Jérémy Sandoz & Max Cigrang & Amélie Zachayus & Philippe Catez & Lise-Marie Donnio & Clèmence Elly & Jadwiga Nieminuszczy & Pietro Berico & Cathy Braun & Sergey Alekseev & Jean-Marc Egly & Wojciech Ni, 2023. "Active mRNA degradation by EXD2 nuclease elicits recovery of transcription after genotoxic stress," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35922-5
    DOI: 10.1038/s41467-023-35922-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-35922-5
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-35922-5?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. Stephen P. Jackson & Jiri Bartek, 2009. "The DNA-damage response in human biology and disease," Nature, Nature, vol. 461(7267), pages 1071-1078, October.
    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. Zita Gál & Stavroula Boukoura & Kezia Catharina Oxe & Sara Badawi & Blanca Nieto & Lea Milling Korsholm & Sille Blangstrup Geisler & Ekaterina Dulina & Anna Vestergaard Rasmussen & Christina Dahl & We, 2024. "Hyper-recombination in ribosomal DNA is driven by long-range resection-independent RAD51 accumulation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Ilaria Rosso & Corey Jones-Weinert & Francesca Rossiello & Matteo Cabrini & Silvia Brambillasca & Leonel Munoz-Sagredo & Zeno Lavagnino & Emanuele Martini & Enzo Tedone & Massimiliano Garre’ & Julio A, 2023. "Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Halh Al-Serori & Franziska Ferk & Michael Kundi & Andrea Bileck & Christopher Gerner & Miroslav Mišík & Armen Nersesyan & Monika Waldherr & Manuel Murbach & Tamara T Lah & Christel Herold-Mende & Andr, 2018. "Mobile phone specific electromagnetic fields induce transient DNA damage and nucleotide excision repair in serum-deprived human glioblastoma cells," PLOS ONE, Public Library of Science, vol. 13(4), pages 1-17, April.
    4. Daipayan Banerjee & Kurt Langberg & Salar Abbas & Eric Odermatt & Praveen Yerramothu & Martin Volaric & Matthew A. Reidenbach & Kathy J. Krentz & C. Dustin Rubinstein & David L. Brautigan & Tarek Abba, 2021. "A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    5. Jenny Kaur Singh & Rebecca Smith & Magdalena B. Rother & Anton J. L. Groot & Wouter W. Wiegant & Kees Vreeken & Ostiane D’Augustin & Robbert Q. Kim & Haibin Qian & Przemek M. Krawczyk & Román González, 2021. "Zinc finger protein ZNF384 is an adaptor of Ku to DNA during classical non-homologous end-joining," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    6. Miho M. Suzuki & Kenta Iijima & Koichi Ogami & Keiko Shinjo & Yoshiteru Murofushi & Jingqi Xie & Xuebing Wang & Yotaro Kitano & Akira Mamiya & Yuji Kibe & Tatsunori Nishimura & Fumiharu Ohka & Ryuta S, 2023. "TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    7. Ye Cai & Huifen Cao & Fang Wang & Yufei Zhang & Philipp Kapranov, 2022. "Complex genomic patterns of abasic sites in mammalian DNA revealed by a high-resolution SSiNGLe-AP method," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    8. Sidrah Shah & Alison Cheung & Mikolaj Kutka & Matin Sheriff & Stergios Boussios, 2022. "Epithelial Ovarian Cancer: Providing Evidence of Predisposition Genes," IJERPH, MDPI, vol. 19(13), pages 1-14, July.
    9. Jessica D. Tischler & Hiroshi Tsuchida & Rosevalentine Bosire & Tommy T. Oda & Ana Park & Richard O. Adeyemi, 2024. "FLIP(C1orf112)-FIGNL1 complex regulates RAD51 chromatin association to promote viability after replication stress," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    10. Lin-Lin Zhou & Tao Zhang & Yun Xue & Chuan Yue & Yihui Pan & Pengyu Wang & Teng Yang & Meixia Li & Hu Zhou & Kan Ding & Jianhua Gan & Hongbin Ji & Cai-Guang Yang, 2023. "Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    11. Daniel Gómez-Cabello & George Pappas & Diana Aguilar-Morante & Christoffel Dinant & Jiri Bartek, 2022. "CtIP-dependent nascent RNA expression flanking DNA breaks guides the choice of DNA repair pathway," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    12. Pedro Weickert & Hao-Yi Li & Maximilian J. Götz & Sophie Dürauer & Denitsa Yaneva & Shubo Zhao & Jacqueline Cordes & Aleida C. Acampora & Ignasi Forne & Axel Imhof & Julian Stingele, 2023. "SPRTN patient variants cause global-genome DNA-protein crosslink repair defects," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    13. Pradeep Ramalingam & Michael C. Gutkin & Michael G. Poulos & Taylor Tillery & Chelsea Doughty & Agatha Winiarski & Ana G. Freire & Shahin Rafii & David Redmond & Jason M. Butler, 2023. "Restoring bone marrow niche function rejuvenates aged hematopoietic stem cells by reactivating the DNA Damage Response," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    14. Ross J. Hill & Nazareno Bona & Job Smink & Hannah K. Webb & Alastair Crisp & Juan I. Garaycoechea & Gerry P. Crossan, 2024. "p53 regulates diverse tissue-specific outcomes to endogenous DNA damage in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    15. Andrea M. Kaminski & Kishore K. Chiruvella & Dale A. Ramsden & Katarzyna Bebenek & Thomas A. Kunkel & Lars C. Pedersen, 2022. "Analysis of diverse double-strand break synapsis with Polλ reveals basis for unique substrate specificity in nonhomologous end-joining," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    16. Najmeh Soltanmohammadi & Siyao Wang & Björn Schumacher, 2022. "Somatic PMK-1/p38 signaling links environmental stress to germ cell apoptosis and heritable euploidy," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    17. Aldo S. Bader & Martin Bushell, 2023. "iMUT-seq: high-resolution DSB-induced mutation profiling reveals prevalent homologous-recombination dependent mutagenesis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    18. Felix M. Dobbs & Patrick Eijk & Mick D. Fellows & Luisa Loiacono & Roberto Nitsch & Simon H. Reed, 2022. "Precision digital mapping of endogenous and induced genomic DNA breaks by INDUCE-seq," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    19. Qin Qin & Jing Lu & Hongcheng Zhu & Liping Xu & Hongyan Cheng & Liangliang Zhan & Xi Yang & Chi Zhang & Xinchen Sun, 2014. "PARP-1 Val762Ala Polymorphism and Risk of Cancer: A Meta-Analysis Based on 39 Case-Control Studies," PLOS ONE, Public Library of Science, vol. 9(5), pages 1-12, May.
    20. Shrinivas Sudhir Ambekar & Shanta Shrisel Hattur & Prajakta Budha Bule, 2017. "DNA: Damage and Repair Mechanisms in Humans," Global Journal of Pharmacy & Pharmaceutical Sciences, Juniper Publishers Inc., vol. 3(3), pages 58-66, July.

    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_s41467-023-35922-5. 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.