IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-37109-4.html
   My bibliography  Save this article

Structural basis of Ty1 integrase tethering to RNA polymerase III for targeted retrotransposon integration

Author

Listed:
  • Phong Quoc Nguyen

    (Centro de Investigaciones Biológicas Margarita Salas, CSIC
    Aix-Marseille Université, CNRS, AFMB UMR 7257)

  • Sonia Huecas

    (Centro de Investigaciones Biológicas Margarita Salas, CSIC)

  • Amna Asif-Laidin

    (Université Paris Cité, IRSL, Inserm, U944, CNRS, UMR7212)

  • Adrián Plaza-Pegueroles

    (Centro de Investigaciones Biológicas Margarita Salas, CSIC)

  • Beatrice Capuzzi

    (Université Paris Cité, IRSL, Inserm, U944, CNRS, UMR7212)

  • Noé Palmic

    (Université Paris Cité, IRSL, Inserm, U944, CNRS, UMR7212)

  • Christine Conesa

    (Institute for Integrative Biology of the Cell (I2BC))

  • Joël Acker

    (Institute for Integrative Biology of the Cell (I2BC))

  • Juan Reguera

    (Aix-Marseille Université, CNRS, AFMB UMR 7257
    INSERM, AFMB UMR7257)

  • Pascale Lesage

    (Université Paris Cité, IRSL, Inserm, U944, CNRS, UMR7212)

  • Carlos Fernández-Tornero

    (Centro de Investigaciones Biológicas Margarita Salas, CSIC)

Abstract

The yeast Ty1 retrotransposon integrates upstream of genes transcribed by RNA polymerase III (Pol III). Specificity of integration is mediated by an interaction between the Ty1 integrase (IN1) and Pol III, currently uncharacterized at the atomic level. We report cryo-EM structures of Pol III in complex with IN1, revealing a 16-residue segment at the IN1 C-terminus that contacts Pol III subunits AC40 and AC19, an interaction that we validate by in vivo mutational analysis. Binding to IN1 associates with allosteric changes in Pol III that may affect its transcriptional activity. The C-terminal domain of subunit C11, involved in RNA cleavage, inserts into the Pol III funnel pore, providing evidence for a two-metal mechanism during RNA cleavage. Additionally, ordering next to C11 of an N-terminal portion from subunit C53 may explain the connection between these subunits during termination and reinitiation. Deletion of the C53 N-terminal region leads to reduced chromatin association of Pol III and IN1, and a major fall in Ty1 integration events. Our data support a model in which IN1 binding induces a Pol III configuration that may favor its retention on chromatin, thereby improving the likelihood of Ty1 integration.

Suggested Citation

  • Phong Quoc Nguyen & Sonia Huecas & Amna Asif-Laidin & Adrián Plaza-Pegueroles & Beatrice Capuzzi & Noé Palmic & Christine Conesa & Joël Acker & Juan Reguera & Pascale Lesage & Carlos Fernández-Tornero, 2023. "Structural basis of Ty1 integrase tethering to RNA polymerase III for targeted retrotransposon integration," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37109-4
    DOI: 10.1038/s41467-023-37109-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-37109-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-37109-4?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. Florian B. Heiss & Julia L. Daiß & Philipp Becker & Christoph Engel, 2021. "Conserved strategies of RNA polymerase I hibernation and activation," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    2. Guillermo Abascal-Palacios & Ewan Phillip Ramsay & Fabienne Beuron & Edward Morris & Alessandro Vannini, 2018. "Structural basis of RNA polymerase III transcription initiation," Nature, Nature, vol. 553(7688), pages 301-306, January.
    3. Guillermo Abascal-Palacios & Laura Jochem & Carlos Pla-Prats & Fabienne Beuron & Alessandro Vannini, 2021. "Structural basis of Ty3 retrotransposon integration at RNA Polymerase III-transcribed genes," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    4. Saurabh Mishra & Shaina H. Hasan & Rima M. Sakhawala & Shereen Chaudhry & Richard J. Maraia, 2021. "Mechanism of RNA polymerase III termination-associated reinitiation-recycling conferred by the essential function of the N terminal-and-linker domain of the C11 subunit," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    5. Alan C. M. Cheung & Patrick Cramer, 2011. "Structural basis of RNA polymerase II backtracking, arrest and reactivation," Nature, Nature, vol. 471(7337), pages 249-253, March.
    6. Niklas A. Hoffmann & Arjen J. Jakobi & María Moreno-Morcillo & Sebastian Glatt & Jan Kosinski & Wim J. H. Hagen & Carsten Sachse & Christoph W. Müller, 2015. "Molecular structures of unbound and transcribing RNA polymerase III," Nature, Nature, vol. 528(7581), pages 231-236, December.
    7. Matthias K. Vorländer & Heena Khatter & Rene Wetzel & Wim J. H. Hagen & Christoph W. Müller, 2018. "Molecular mechanism of promoter opening by RNA polymerase III," Nature, Nature, vol. 553(7688), pages 295-300, January.
    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. Saurabh Mishra & Shaina H. Hasan & Rima M. Sakhawala & Shereen Chaudhry & Richard J. Maraia, 2021. "Mechanism of RNA polymerase III termination-associated reinitiation-recycling conferred by the essential function of the N terminal-and-linker domain of the C11 subunit," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    2. Haifeng Hou & Yan Li & Mo Wang & Aijun Liu & Zishuo Yu & Ke Chen & Dan Zhao & Yanhui Xu, 2021. "Structural insights into RNA polymerase III-mediated transcription termination through trapping poly-deoxythymidine," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    3. Kevin Van Bortle & David P. Marciano & Qing Liu & Tristan Chou & Andrew M. Lipchik & Sanjay Gollapudi & Benjamin S. Geller & Emma Monte & Rohinton T. Kamakaka & Michael P. Snyder, 2022. "A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Guillermo Abascal-Palacios & Laura Jochem & Carlos Pla-Prats & Fabienne Beuron & Alessandro Vannini, 2021. "Structural basis of Ty3 retrotransposon integration at RNA Polymerase III-transcribed genes," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    5. Lisa-Marie Appel & Vedran Franke & Johannes Benedum & Irina Grishkovskaya & Xué Strobl & Anton Polyansky & Gregor Ammann & Sebastian Platzer & Andrea Neudolt & Anna Wunder & Lena Walch & Stefanie Kais, 2023. "The SPOC domain is a phosphoserine binding module that bridges transcription machinery with co- and post-transcriptional regulators," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    6. Joseph G. Beton & Thomas Mulvaney & Tristan Cragnolini & Maya Topf, 2024. "Cryo-EM structure and B-factor refinement with ensemble representation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Simona Pilotto & Michal Sýkora & Gwenny Cackett & Christopher Dulson & Finn Werner, 2024. "Structure of the recombinant RNA polymerase from African Swine Fever Virus," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Lisa-Marie Appel & Vedran Franke & Melania Bruno & Irina Grishkovskaya & Aiste Kasiliauskaite & Tanja Kaufmann & Ursula E. Schoeberl & Martin G. Puchinger & Sebastian Kostrhon & Carmen Ebenwaldner & M, 2021. "PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    9. Zakia Morichaud & Stefano Trapani & Rishi K. Vishwakarma & Laurent Chaloin & Corinne Lionne & Joséphine Lai-Kee-Him & Patrick Bron & Konstantin Brodolin, 2023. "Structural basis of the mycobacterial stress-response RNA polymerase auto-inhibition via oligomerization," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    10. Allison Ballandras-Colas & Vidya Chivukula & Dominika T. Gruszka & Zelin Shan & Parmit K. Singh & Valerie E. Pye & Rebecca K. McLean & Gregory J. Bedwell & Wen Li & Andrea Nans & Nicola J. Cook & Hind, 2022. "Multivalent interactions essential for lentiviral integrase function," Nature Communications, Nature, vol. 13(1), pages 1-16, 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_s41467-023-37109-4. 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.