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Nat Commun. 2017 Oct 26;8(1):1145. doi: 10.1038/s41467-017-01196-x.

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

Author information

1
Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, HMS Initiative for RNA Medicine, Boston, MA, 02115, USA.
2
Vishuo Biomedical, #3-33 Teletech Park, 20 Science Park Road, Singapore, 117674, Singapore.
3
Department of Drug Sciences, University of Pavia, Pavia, 27100, Italy.
4
Beijing Genomics Institute, Shenzhen, 518083, China.
5
Department of Neurology and Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Charlestown, MA, 02129, USA.
6
Neurosurgery Department, University of Minnesota, Minneapolis, MN, 55455, USA.
7
Department of Neurosurgery, University of California, La Jolla, San Diego, CA, 92093, USA.
8
Scintillon Institute, San Diego, CA, 92121, USA.
9
Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, HMS Initiative for RNA Medicine, Boston, MA, 02115, USA. akrichevsky@bwh.harvard.edu.

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.

PMID:
29074968
PMCID:
PMC5658400
DOI:
10.1038/s41467-017-01196-x
[Indexed for MEDLINE]
Free PMC Article

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