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Girolline is a sequence context-selective modulator of eIF5A activity

Author

Listed:
  • Tilman Schneider-Poetsch

    (Wako)

  • Yongjun Dang

    (Chongqing Medical University)

  • Wakana Iwasaki

    (RIKEN Center for Biosystems Dynamics Research)

  • Mayumi Arata

    (Wako)

  • Yuichi Shichino

    (Wako)

  • Ali Al Mourabit

    (Université Paris-Saclay)

  • Celine Moriou

    (Université Paris-Saclay)

  • Daniel Romo

    (One Bear Place)

  • Jun O. Liu

    (The Johns Hopkins University School of Medicine)

  • Takuhiro Ito

    (RIKEN Center for Biosystems Dynamics Research)

  • Shintaro Iwasaki

    (Wako
    Kashiwa)

  • Minoru Yoshida

    (Wako
    Wako
    Bunkyo-ku
    Bunkyo-ku)

Abstract

Natural products have a long history of providing probes into protein biosynthesis, with many of these compounds serving as therapeutics. The marine natural product girolline has been described as an inhibitor of protein synthesis. Its precise mechanism of action, however, has remained unknown. The data we present here suggests that girolline is a sequence-selective modulator of translation factor eIF5A. Girolline interferes with ribosome-eIF5A interaction and induces ribosome stalling where translational progress is impeded, including on AAA-encoded lysine. Our data furthermore indicate that eIF5A plays a physiological role in ribosome-associated quality control and in maintaining the efficiency of translational progress. Girolline helped to deepen our understanding of the interplay between protein production and quality control in a physiological setting and offers a potent chemical tool to selectively modulate gene expression.

Suggested Citation

  • Tilman Schneider-Poetsch & Yongjun Dang & Wakana Iwasaki & Mayumi Arata & Yuichi Shichino & Ali Al Mourabit & Celine Moriou & Daniel Romo & Jun O. Liu & Takuhiro Ito & Shintaro Iwasaki & Minoru Yoshid, 2025. "Girolline is a sequence context-selective modulator of eIF5A activity," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-54838-2
    DOI: 10.1038/s41467-024-54838-2
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    References listed on IDEAS

    as
    1. Shintaro Iwasaki & Stephen N. Floor & Nicholas T. Ingolia, 2016. "Rocaglates convert DEAD-box protein eIF4A into a sequence-selective translational repressor," Nature, Nature, vol. 534(7608), pages 558-561, June.
    2. Maxim S. Svetlov & Timm O. Koller & Sezen Meydan & Vaishnavi Shankar & Dorota Klepacki & Norbert Polacek & Nicholas R. Guydosh & Nora Vázquez-Laslop & Daniel N. Wilson & Alexander S. Mankin, 2021. "Context-specific action of macrolide antibiotics on the eukaryotic ribosome," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Kevin C. Stein & Fabián Morales-Polanco & Joris Lienden & T. Kelly Rainbolt & Judith Frydman, 2022. "Ageing exacerbates ribosome pausing to disrupt cotranslational proteostasis," Nature, Nature, vol. 601(7894), pages 637-642, January.
    4. Preeti Saini & Daniel E. Eyler & Rachel Green & Thomas E. Dever, 2009. "Hypusine-containing protein eIF5A promotes translation elongation," Nature, Nature, vol. 459(7243), pages 118-121, May.
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