Nontemplated Nucleotide Additions Distinguish the Small RNA Composition in Cells from Exosomes

被引:571
作者
Koppers-Lalic, Danijela [1 ,2 ]
Hackenberg, Michael [3 ]
Bijnsdorp, Irene V. [4 ]
van Eijndhoven, Monique A. J. [1 ,2 ]
Sadek, Payman [1 ,2 ]
Sie, Daud [1 ]
Zini, Nicoletta [5 ,6 ]
Middeldorp, Jaap M. [1 ]
Ylstra, Bauke [1 ]
de Menezes, Renee X. [7 ]
Wuerdinger, Thomas [8 ,9 ,10 ]
Meijer, Gerrit A. [1 ]
Pegtel, D. Michiel [1 ,2 ]
机构
[1] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, NL-1007 MB Amsterdam, Netherlands
[2] Vrije Univ Amsterdam, Med Ctr, Exosomes Res Grp, NL-1007 MB Amsterdam, Netherlands
[3] Univ Granada, Dept Genet, Computat Genom & Bioinformat Grp, E-18071 Granada, Spain
[4] Vrije Univ Amsterdam, Med Ctr, Dept Urol, NL-1007 MB Amsterdam, Netherlands
[5] CNR Natl Res Council Italy, IGM, I-40136 Bologna, Italy
[6] IOR, SC Lab Musculoskeletal Cell Biol, I-40136 Bologna, Italy
[7] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands
[8] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, Neurooncol Res Grp, NL-1007 MB Amsterdam, Netherlands
[9] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA
[10] Harvard Univ, Sch Med, Charlestown, MA 02129 USA
关键词
SMALL NONCODING RNA; 3' ADENYLATION; VIRAL MIRNAS; MICRORNA; STABILIZATION; COMPLEXES; VESICLES; DELIVERY; REVEALS; BINDING;
D O I
10.1016/j.celrep.2014.08.027
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Functional biomolecules, including small noncoding RNAs (ncRNAs), are released and transmitted between mammalian cells via extracellular vesicles (EVs), including endosome-derived exosomes. The small RNA composition in cells differs from exosomes, but underlying mechanisms have not been established. We generated small RNA profiles by RNA sequencing (RNA-seq) from a panel of human B cells and their secreted exosomes. A comprehensive bioinformatics and statistical analysis revealed nonrandomly distributed subsets of microRNA (miRNA) species between B cells and exosomes. Unexpectedly, 3' end adenylated miRNAs are relatively enriched in cells, whereas 3' end uridylated isoforms appear overrepresented in exosomes, as validated in naturally occurring EVs isolated from human urine samples. Collectively, our findings suggest that posttranscriptional modifications, notably 3' end adenylation and uridylation, exert opposing effects that may contribute, at least in part, to direct ncRNA sorting into EVs.
引用
收藏
页码:1649 / 1658
页数:10
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