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

共 63 条

[1] tRNA fragments in human health and disease [J].

Anderson, Paul ;

Ivanov, Pavel .

FEBS LETTERS, 2014, 588 (23) :4297-4304

[2]

[Anonymous], REGULATORY RNAS

[3] Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma [J].

Arroyo, Jason D. ;

Chevillet, John R. ;

Kroh, Evan M. ;

Ruf, Ingrid K. ;

Pritchard, Colin C. ;

Gibson, Donald F. ;

Mitchell, Patrick S. ;

Bennett, Christopher F. ;

Pogosova-Agadjanyan, Era L. ;

Stirewalt, Derek L. ;

Tait, Jonathan F. ;

Tewari, Muneesh .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (12) :5003-5008

[4] Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species [J].

Baglio, Serena Rubina ;

Rooijers, Koos ;

Koppers-Lalic, Danijela ;

Verweij, Frederik J. ;

Lanzon, M. Perez ;

Zini, Nicoletta ;

Naaijkens, Benno ;

Perut, Francesca ;

Niessen, Hans W. M. ;

Baldini, Nicola ;

Pegtel, D. Michiel .

STEM CELL RESEARCH & THERAPY, 2015, 6

[5] Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy [J].

Bang, Claudia ;

Batkai, Sandor ;

Dangwal, Seema ;

Gupta, Shashi Kumar ;

Foinquinos, Ariana ;

Holzmann, Angelika ;

Just, Annette ;

Remke, Janet ;

Zimmer, Karina ;

Zeug, Andre ;

Ponimaskin, Evgeni ;

Schmiedl, Andreas ;

Yin, Xiaoke ;

Mayr, Manuel ;

Halder, Rashi ;

Fischer, Andre ;

Engelhardt, Stefan ;

Wei, Yuanyuan ;

Schober, Andreas ;

Fiedler, Jan ;

Thum, Thomas .

JOURNAL OF CLINICAL INVESTIGATION, 2014, 124 (05) :2136-2146

[6] Exosomes secreted by human cells transport largely mRNA fragments that are enriched in the 3′-untranslated regions [J].

Batagov, Arsen O. ;

Kurochkin, Igor V. .

BIOLOGY DIRECT, 2013, 8

[7] Extracellular vesicle-mediated transfer of processed and functional RNY5 RNA [J].

Chakrabortty, Sudipto K. ;

Prakash, Ashwin ;

Nechooshtan, Gal ;

Hearn, Stephen ;

Gingeras, Thomas R. .

RNA, 2015, 21 (11) :1966-1979

[8] Secreted microRNAs: a new form of intercellular communication [J].

Chen, Xi ;

Liang, Hongwei ;

Zhang, Junfeng ;

Zen, Ke ;

Zhang, Chen-Yu .

TRENDS IN CELL BIOLOGY, 2012, 22 (03) :125-132

[9] An RNA Degradation Machine Sculpted by Ro Autoantigen and Noncoding RNA [J].

Chen, Xinguo ;

Taylor, David W. ;

Fowler, Casey C. ;

Galan, Jorge E. ;

Wang, Hong-Wei ;

Wolin, Sandra L. .

CELL, 2013, 153 (01) :166-177

[10] Quantitative and stoichiometric analysis of the microRNA content of exosomes [J].

Chevillet, John R. ;

Kang, Qing ;

Ruf, Ingrid K. ;

Briggs, Hilary A. ;

Vojtech, Lucia N. ;

Hughes, Sean M. ;

Cheng, Heather H. ;

Arroyo, Jason D. ;

Meredith, Emily K. ;

Gallichotte, Emily N. ;

Pogosova-Agadjanyan, Era L. ;

Morrissey, Colm ;

Stirewalt, Derek L. ;

Hladik, Florian ;

Yu, Evan Y. ;

Higano, Celestia S. ;

Tewari, Muneesh .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (41) :14888-14893

← 1 2 3 4 5 6 7 →