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, Anna M. Krichevsky

Research output: Contribution to journalArticlepeer-review

368 Scopus citations

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.

Original languageEnglish (US)
Article number1145
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

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© 2017 The Author(s).

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