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DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions

Author

Listed:
  • Markus Sauer

    (University of Würzburg
    University of Groningen
    University Hospital Bonn)

  • Stefan A. Juranek

    (University Hospital Bonn)

  • James Marks

    (National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH)

  • Alessio Magis

    (University Hospital Bonn)

  • Hinke G. Kazemier

    (University of Groningen)

  • Daniel Hilbig

    (University Hospital Bonn)

  • Daniel Benhalevy

    (National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH)

  • Xiantao Wang

    (National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH)

  • Markus Hafner

    (National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH)

  • Katrin Paeschke

    (University of Würzburg
    University of Groningen
    University Hospital Bonn)

Abstract

Translation efficiency can be affected by mRNA stability and secondary structures, including G-quadruplex structures (G4s). The highly conserved DEAH-box helicase DHX36/RHAU resolves G4s on DNA and RNA in vitro, however a systems-wide analysis of DHX36 targets and function is lacking. We map globally DHX36 binding to RNA in human cell lines and find it preferentially interacting with G-rich and G4-forming sequences on more than 4500 mRNAs. While DHX36 knockout (KO) results in a significant increase in target mRNA abundance, ribosome occupancy and protein output from these targets decrease, suggesting that they were rendered translationally incompetent. Considering that DHX36 targets, harboring G4s, preferentially localize in stress granules, and that DHX36 KO results in increased SG formation and protein kinase R (PKR/EIF2AK2) phosphorylation, we speculate that DHX36 is involved in resolution of rG4 induced cellular stress.

Suggested Citation

  • Markus Sauer & Stefan A. Juranek & James Marks & Alessio Magis & Hinke G. Kazemier & Daniel Hilbig & Daniel Benhalevy & Xiantao Wang & Markus Hafner & Katrin Paeschke, 2019. "DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10432-5
    DOI: 10.1038/s41467-019-10432-5
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    Cited by:

    1. Prakash Kharel & Marta Fay & Ekaterina V. Manasova & Paul J. Anderson & Alexander V. Kurkin & Junjie U. Guo & Pavel Ivanov, 2023. "Stress promotes RNA G-quadruplex folding in human cells," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Sarah Rösing & Fabian Ullrich & Susann Meisterfeld & Franziska Schmidt & Laura Mlitzko & Marijana Croon & Ryan G Nattrass & Nadia Eberl & Julia Mahlberg & Martin Schlee & Anja Wieland & Philipp Simon , 2024. "Chronic endoplasmic reticulum stress in myotonic dystrophy type 2 promotes autoimmunity via mitochondrial DNA release," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Yuwei Zhang & Jieyu Zhao & Xiaona Chen & Yulong Qiao & Jinjin Kang & Xiaofan Guo & Feng Yang & Kaixin Lyu & Yiliang Ding & Yu Zhao & Hao Sun & Chun-Kit Kwok & Huating Wang, 2024. "DHX36 binding induces RNA structurome remodeling and regulates RNA abundance via m6A reader YTHDF1," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Chun-Ying Lee & Meera Joshi & Ashley Wang & Sua Myong, 2024. "5′UTR G-quadruplex structure enhances translation in size dependent manner," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Alessio Magis & Michaela Limmer & Venkat Mudiyam & David Monchaud & Stefan Juranek & Katrin Paeschke, 2023. "UV-induced G4 DNA structures recruit ZRF1 which prevents UV-induced senescence," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Pablo Gómez-del Arco & Joan Isern & Daniel Jimenez-Carretero & Dolores López-Maderuelo & Rebeca Piñeiro-Sabarís & Fadoua El Abdellaoui-Soussi & Carlos Torroja & María Linarejos Vera-Pedrosa & Mercedes, 2024. "The G4 resolvase Dhx36 modulates cardiomyocyte differentiation and ventricular conduction system development," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    7. Anna C. Papageorgiou & Michaela Pospisilova & Jakub Cibulka & Raghib Ashraf & Christopher A. Waudby & Pavel Kadeřávek & Volha Maroz & Karel Kubicek & Zbynek Prokop & Lumir Krejci & Konstantinos Tripsi, 2023. "Recognition and coacervation of G-quadruplexes by a multifunctional disordered region in RECQ4 helicase," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    8. Matthias M. Zimmer & Anuja Kibe & Ulfert Rand & Lukas Pekarek & Liqing Ye & Stefan Buck & Redmond P. Smyth & Luka Cicin-Sain & Neva Caliskan, 2021. "The short isoform of the host antiviral protein ZAP acts as an inhibitor of SARS-CoV-2 programmed ribosomal frameshifting," Nature Communications, Nature, vol. 12(1), pages 1-15, December.

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