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

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 and Anna M. Krichevsky ()
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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
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

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01196-x

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