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Coding and noncoding landscape of extracellular RNA released by human glioma stem cells

Author

Listed:
  • Zhiyun Wei

    (Brigham and Women’s Hospital and Harvard Medical School, HMS Initiative for RNA Medicine)

  • Arsen O. Batagov

    (Vishuo Biomedical)

  • Sergio Schinelli

    (University of Pavia)

  • Jintu Wang

    (Beijing Genomics Institute)

  • Yang Wang

    (Brigham and Women’s Hospital and Harvard Medical School, HMS Initiative for RNA Medicine)

  • Rachid El Fatimy

    (Brigham and Women’s Hospital and Harvard Medical School, HMS Initiative for RNA Medicine)

  • Rosalia Rabinovsky

    (Brigham and Women’s Hospital and Harvard Medical School, HMS Initiative for RNA Medicine)

  • Leonora Balaj

    (Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School)

  • Clark C. Chen

    (University of Minnesota)

  • Fred Hochberg

    (University of California
    Scintillon Institute)

  • Bob Carter

    (University of California)

  • Xandra O. Breakefield

    (Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School)

  • Anna M. Krichevsky

    (Brigham and Women’s Hospital and Harvard Medical School, HMS Initiative for RNA Medicine)

Abstract

Tumor-released RNA may mediate intercellular communication and serve as biomarkers. Here we develop a protocol enabling quantitative, minimally biased analysis of extracellular RNAs (exRNAs) associated with microvesicles, exosomes (collectively called EVs), and ribonucleoproteins (RNPs). The exRNA complexes isolated from patient-derived glioma stem-like cultures exhibit distinct compositions, with microvesicles most closely reflecting cellular transcriptome. exRNA is enriched in small ncRNAs, such as miRNAs in exosomes, and precisely processed tRNA and Y RNA fragments in EVs and exRNPs. EV-enclosed mRNAs are mostly fragmented, and UTRs enriched; nevertheless, some full-length mRNAs are present. Overall, there is less than one copy of non-rRNA per EV. Our results suggest that massive EV/exRNA uptake would be required to ensure functional impact of transferred RNA on brain recipient cells and predict the most impactful miRNAs in such conditions. This study also provides a catalog of diverse exRNAs useful for biomarker discovery and validates its feasibility on cerebrospinal fluid.

Suggested Citation

  • Zhiyun Wei & Arsen O. Batagov & Sergio Schinelli & Jintu Wang & Yang Wang & Rachid El Fatimy & Rosalia Rabinovsky & Leonora Balaj & Clark C. Chen & Fred Hochberg & Bob Carter & Xandra O. Breakefield &, 2017. "Coding and noncoding landscape of extracellular RNA released by human glioma stem cells," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01196-x
    DOI: 10.1038/s41467-017-01196-x
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