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The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs

Author

Listed:
  • Dario Dattilo

    (Sapienza University of Rome)

  • Gaia Di Timoteo

    (Sapienza University of Rome)

  • Adriano Setti

    (Sapienza University of Rome)

  • Andrea Giuliani

    (Sapienza University of Rome)

  • Giovanna Peruzzi

    (Center for Life Nano- & Neuro-Science@Sapienza, Fondazione Istituto Italiano di Tecnologia (IIT))

  • Manuel Beltran Nebot

    (Sapienza University of Rome)

  • Alvaro Centrón-Broco

    (Sapienza University of Rome)

  • Davide Mariani

    (Center for Human Technologies@Istituto Italiano di Tecnologia (IIT))

  • Chiara Mozzetta

    (Institute of Molecular Biology and Pathology (IBPM), National Research Council (CNR) of Italy)

  • Irene Bozzoni

    (Sapienza University of Rome
    Center for Life Nano- & Neuro-Science@Sapienza, Fondazione Istituto Italiano di Tecnologia (IIT)
    Center for Human Technologies@Istituto Italiano di Tecnologia (IIT))

Abstract

N6-Methyladenosine (m6A) is well-known for controlling different processes of linear RNA metabolism. Conversely, its role in the biogenesis and function of circular RNAs (circRNAs) is still poorly understood. Here, we characterize circRNA expression in the pathological context of rhabdomyosarcoma (RMS), observing a global increase when compared to wild-type myoblasts. For a set of circRNAs, such an increase is due to the raised expression of the m6A machinery, which we also find to control the proliferation activity of RMS cells. Furthermore, we identify the RNA helicase DDX5 as a mediator of the back-splicing reaction and as a co-factor of the m6A regulatory network. DDX5 and the m6A reader YTHDC1 are shown to interact and to promote the production of a common subset of circRNAs in RMS. In line with the observation that YTHDC1/DDX5 depletion reduces RMS proliferation, our results provide proteins and RNA candidates for the study of rhabdomyosarcoma tumorigenicity.

Suggested Citation

  • Dario Dattilo & Gaia Di Timoteo & Adriano Setti & Andrea Giuliani & Giovanna Peruzzi & Manuel Beltran Nebot & Alvaro Centrón-Broco & Davide Mariani & Chiara Mozzetta & Irene Bozzoni, 2023. "The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37578-7
    DOI: 10.1038/s41467-023-37578-7
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    References listed on IDEAS

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    1. Lorenzo Errichelli & Stefano Dini Modigliani & Pietro Laneve & Alessio Colantoni & Ivano Legnini & Davide Capauto & Alessandro Rosa & Riccardo De Santis & Rebecca Scarfò & Giovanna Peruzzi & Lei Lu & , 2017. "FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
    2. Ri-Xin Chen & Xin Chen & Liang-Ping Xia & Jia-Xing Zhang & Zhi-Zhong Pan & Xiao-Dan Ma & Kai Han & Jie-Wei Chen & Jean-Gabrie Judde & Olivier Deas & Feng Wang & Ning-Fang Ma & Xinyuan Guan & Jing-Ping, 2019. "N6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    3. Hiroshi I. Suzuki & Kaoru Yamagata & Koichi Sugimoto & Takashi Iwamoto & Shigeaki Kato & Kohei Miyazono, 2009. "Modulation of microRNA processing by p53," Nature, Nature, vol. 460(7254), pages 529-533, July.
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