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

被引：394

作者：

Wei, Zhiyun ^{[1
,2
]}

Batagov, Arsen O. ^{[3
]}

Schinelli, Sergio ^{[4
]}

Wang, Jintu ^{[5
]}

Wang, Yang ^{[1
,2
]}

El Fatimy, Rachid ^{[1
,2
]}

Rabinovsky, Rosalia ^{[1
,2
]}

Balaj, Leonora ^{[6
,7
]}

Chen, Clark C. ^{[8
]}

Hochberg, Fred ^{[9
,10
]}

Carter, Bob ^{[9
]}

Breakefield, Xandra O. ^{[6
,7
]}

Krichevsky, Anna M. ^{[1
,2
]}

机构：

[1] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA

[2] Harvard Med Sch, HMS Initiat RNA Med, Boston, MA 02115 USA

[3] Vishuo Biomed, 3-33 Teletech Pk,20 Sci Pk Rd, Singapore 117674, Singapore

[4] Univ Pavia, Dept Drug Sci, I-27100 Pavia, Italy

[5] Beijing Genom Inst, Shenzhen 518083, Peoples R China

[6] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol & Radiol, Charlestown, MA 02129 USA

[7] Harvard Med Sch, Program Neurosci, Charlestown, MA 02129 USA

[8] Univ Minnesota, Neurosurg Dept, Minneapolis, MN 55455 USA

[9] Univ Calif San Diego, Dept Neurosurg, San Diego, CA 92093 USA

[10] Scintillon Inst, San Diego, CA 92121 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

MEDIATED TRANSFER; Y RNAS; MICRORNAS; EXPRESSION; EXOSOMES; VESICLES; ANGIOGENIN; FRAGMENTS; CARRY; COMMUNICATION;

D O I：

10.1038/s41467-017-01196-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：15

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