Z. Wei, A. O. Batagov, S. Schinelli, J. Wang, Y. Wang, R. El Fatimy, R. Rabinovsky, L. Balaj, C. C. Chen, F. Hochberg, B. Carter, X. O. Breakefield, and A. M. Krichevsky. Coding and noncoding landscape of extracellular RNA released by human glioma stem cells. Nat Commun, 8(1):1145, 10 2017. [PubMed Central:\href https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658400PMC5658400] [DOI:\href https://dx.doi.org/10.1038/s41467-017-01196-x10.1038/s41467-017-01196-x] [PubMed:\href https://www.ncbi.nlm.nih.gov/pubmed/2518495125184951].


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.