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Space radiation damage rescued by inhibition of key spaceflight associated miRNAs

Author

Listed:
  • J. Tyson McDonald

    (Georgetown University School of Medicine)

  • JangKeun Kim

    (Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine)

  • Lily Farmerie

    (Vascular Medicine Institute at the University of Pittsburgh Department of Medicine
    University of Pittsburgh)

  • Meghan L. Johnson

    (Vascular Medicine Institute at the University of Pittsburgh Department of Medicine)

  • Nidia S. Trovao

    (Fogarty International Center, National Institutes of Health)

  • Shehbeel Arif

    (Children’s Hospital of Philadelphia
    Children’s Hospital of Philadelphia)

  • Keith Siew

    (University College London)

  • Sergey Tsoy

    (Weill Cornell Medicine)

  • Yaron Bram

    (Weill Cornell Medicine)

  • Jiwoon Park

    (Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine)

  • Eliah Overbey

    (Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine)

  • Krista Ryon

    (Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine)

  • Jeffrey Haltom

    (The Children’s Hospital of Philadelphia)

  • Urminder Singh

    (Iowa State University)

  • Francisco J. Enguita

    (Universidade de Lisboa)

  • Victoria Zaksas

    (University of Chicago
    Clever Research Lab)

  • Joseph W. Guarnieri

    (The Children’s Hospital of Philadelphia)

  • Michael Topper

    (The Johns Hopkins Medical Institutions)

  • Douglas C. Wallace

    (The Children’s Hospital of Philadelphia
    University of Pennsylvania School of Medicine)

  • Cem Meydan

    (Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine)

  • Stephen Baylin

    (The Johns Hopkins Medical Institutions)

  • Robert Meller

    (Morehouse School of Medicine)

  • Masafumi Muratani

    (University of Tsukuba
    University of Tsukuba)

  • D. Marshall Porterfield

    (Purdue University)

  • Brett Kaufman

    (Vascular Medicine Institute at the University of Pittsburgh Department of Medicine
    University of Pittsburgh)

  • Marcelo A. Mori

    (Universidade Estadual de Campinas
    Universidade Estadual de Campinas)

  • Stephen B. Walsh

    (University College London)

  • Dominique Sigaudo-Roussel

    (Université Claude Bernard Lyon 1)

  • Saida Mebarek

    (Université Claude Bernard Lyon 1)

  • Massimo Bottini

    (University of Rome Tor Vergata)

  • Christophe A. Marquette

    (Université Claude Bernard Lyon 1)

  • Eve Syrkin Wurtele

    (Iowa State University
    Iowa State University)

  • Robert E. Schwartz

    (Weill Cornell Medicine)

  • Diego Galeano

    (Universidad Nacional de Asunción)

  • Christopher E. Mason

    (Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine)

  • Peter Grabham

    (Columbia University)

  • Afshin Beheshti

    (Broad Institute of MIT and Harvard
    Space Biosciences Division, NASA Ames Research Center)

Abstract

Our previous research revealed a key microRNA signature that is associated with spaceflight that can be used as a biomarker and to develop countermeasure treatments to mitigate the damage caused by space radiation. Here, we expand on this work to determine the biological factors rescued by the countermeasure treatment. We performed RNA-sequencing and transcriptomic analysis on 3D microvessel cell cultures exposed to simulated deep space radiation (0.5 Gy of Galactic Cosmic Radiation) with and without the antagonists to three microRNAs: miR-16-5p, miR-125b-5p, and let-7a-5p (i.e., antagomirs). Significant reduction of inflammation and DNA double strand breaks (DSBs) activity and rescue of mitochondria functions are observed after antagomir treatment. Using data from astronaut participants in the NASA Twin Study, Inspiration4, and JAXA missions, we reveal the genes and pathways implicated in the action of these antagomirs are altered in humans. Our findings indicate a countermeasure strategy that can potentially be utilized by astronauts in spaceflight missions to mitigate space radiation damage.

Suggested Citation

  • J. Tyson McDonald & JangKeun Kim & Lily Farmerie & Meghan L. Johnson & Nidia S. Trovao & Shehbeel Arif & Keith Siew & Sergey Tsoy & Yaron Bram & Jiwoon Park & Eliah Overbey & Krista Ryon & Jeffrey Hal, 2024. "Space radiation damage rescued by inhibition of key spaceflight associated miRNAs," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48920-y
    DOI: 10.1038/s41467-024-48920-y
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    References listed on IDEAS

    as
    1. Daehyun Baek & Judit Villén & Chanseok Shin & Fernando D. Camargo & Steven P. Gygi & David P. Bartel, 2008. "The impact of microRNAs on protein output," Nature, Nature, vol. 455(7209), pages 64-71, September.
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    3. Victor Ambros, 2004. "The functions of animal microRNAs," Nature, Nature, vol. 431(7006), pages 350-355, September.
    4. Carsten Sticht & Carolina De La Torre & Alisha Parveen & Norbert Gretz, 2018. "miRWalk: An online resource for prediction of microRNA binding sites," PLOS ONE, Public Library of Science, vol. 13(10), pages 1-6, October.
    Full references (including those not matched with items on IDEAS)

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