IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51343-4.html
   My bibliography  Save this article

Endocytosed dsRNAs induce lysosomal membrane permeabilization that allows cytosolic dsRNA translocation for Drosophila RNAi responses

Author

Listed:
  • Tsubasa Tanaka

    (Kumamoto University
    Kumamoto University)

  • Tamaki Yano

    (Tohoku University)

  • Shingo Usuki

    (Kumamoto University)

  • Yoko Seo

    (Kumamoto University
    Kumamoto University)

  • Kento Mizuta

    (Kumamoto University
    Kumamoto University)

  • Maho Okaguchi

    (Kumamoto University
    Kumamoto University)

  • Maki Yamaguchi

    (Kumamoto University
    Kumamoto University)

  • Kazuko Hanyu-Nakamura

    (Kumamoto University)

  • Noriko Toyama-Sorimachi

    (The University of Tokyo (IMSUT))

  • Katja Brückner

    (University of California San Francisco)

  • Akira Nakamura

    (Kumamoto University
    Kumamoto University)

Abstract

RNA interference (RNAi) is a gene-silencing mechanism triggered by the cytosolic entry of double-stranded RNAs (dsRNAs). Many animal cells internalize extracellular dsRNAs via endocytosis for RNAi induction. However, it is not clear how the endocytosed dsRNAs are translocated into the cytosol across the endo/lysosomal membrane. Herein, we show that in Drosophila S2 cells, endocytosed dsRNAs induce lysosomal membrane permeabilization (LMP) that allows cytosolic dsRNA translocation. LMP mediated by dsRNAs requires the lysosomal Cl−/H+ antiporter ClC-b/DmOstm1. In clc-b or dmostm1 knockout S2 cells, extracellular dsRNAs are endocytosed and reach the lysosomes normally but fail to enter the cytosol. Pharmacological induction of LMP restores extracellular dsRNA-directed RNAi in clc-b or dmostm1-knockout cells. Furthermore, clc-b or dmostm1 mutant flies are defective in extracellular dsRNA-directed RNAi and its associated antiviral immunity. Therefore, endocytosed dsRNAs have an intrinsic ability to induce ClC-b/DmOstm1-dependent LMP that allows cytosolic dsRNA translocation for RNAi responses in Drosophila cells.

Suggested Citation

  • Tsubasa Tanaka & Tamaki Yano & Shingo Usuki & Yoko Seo & Kento Mizuta & Maho Okaguchi & Maki Yamaguchi & Kazuko Hanyu-Nakamura & Noriko Toyama-Sorimachi & Katja Brückner & Akira Nakamura, 2024. "Endocytosed dsRNAs induce lysosomal membrane permeabilization that allows cytosolic dsRNA translocation for Drosophila RNAi responses," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51343-4
    DOI: 10.1038/s41467-024-51343-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51343-4
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-51343-4?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. Maria-Carla Saleh & Michel Tassetto & Ronald P. van Rij & Bertsy Goic & Valérie Gausson & Bassam Berry & Caroline Jacquier & Christophe Antoniewski & Raul Andino, 2009. "Antiviral immunity in Drosophila requires systemic RNA interference spread," Nature, Nature, vol. 458(7236), pages 346-350, March.
    2. Yoshinori Kawamura & Kuniaki Saito & Taishin Kin & Yukiteru Ono & Kiyoshi Asai & Takafumi Sunohara & Tomoko N. Okada & Mikiko C. Siomi & Haruhiko Siomi, 2008. "Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells," Nature, Nature, vol. 453(7196), pages 793-797, June.
    3. Philipp F. Lange & Lena Wartosch & Thomas J. Jentsch & Jens C. Fuhrmann, 2006. "ClC-7 requires Ostm1 as a β-subunit to support bone resorption and lysosomal function," Nature, Nature, vol. 440(7081), pages 220-223, March.
    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. Marianne Yoth & Stéphanie Maupetit-Méhouas & Abdou Akkouche & Nathalie Gueguen & Benjamin Bertin & Silke Jensen & Emilie Brasset, 2023. "Reactivation of a somatic errantivirus and germline invasion in Drosophila ovaries," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Bert I. Crawford & Mary Jo Talley & Joshua Russman & James Riddle & Sabrina Torres & Troy Williams & Michelle S. Longworth, 2024. "Condensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Shengzhang Dong & George Dimopoulos, 2023. "Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality," Nature Communications, Nature, vol. 14(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:15:y:2024:i:1:d:10.1038_s41467-024-51343-4. 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.