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Cell Rep. 2014 Sep 25;8(6):1649-58. doi: 10.1016/j.celrep.2014.08.027. Epub 2014 Sep 18.

Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes.

Author information

1
Department of Pathology, VU University Medical Center, 1007MB Amsterdam, the Netherlands; Exosomes Research Group, VU University Medical Center, 1007MB Amsterdam, the Netherlands. Electronic address: d.koppers@vumc.nl.
2
Department of Genetics, Computational Genomics and Bioinformatics Group, University of Granada, Granada 18071, Spain.
3
Department of Urology, VU University Medical Center, 1007MB Amsterdam, the Netherlands.
4
Department of Pathology, VU University Medical Center, 1007MB Amsterdam, the Netherlands; Exosomes Research Group, VU University Medical Center, 1007MB Amsterdam, the Netherlands.
5
Department of Pathology, VU University Medical Center, 1007MB Amsterdam, the Netherlands.
6
CNR-National Research Council of Italy, IGM, and SC Laboratory of Musculoskeletal Cell Biology, IOR, 40136 Bologna, Italy.
7
Department of Epidemiology and Biostatistics, VU University Medical Center, 1007MB Amsterdam, the Netherlands.
8
Department of Neurosurgery, Neuro-Oncology Research Group, VU University Medical Center, 1007MB Amsterdam, the Netherlands; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
9
Department of Pathology, VU University Medical Center, 1007MB Amsterdam, the Netherlands; Exosomes Research Group, VU University Medical Center, 1007MB Amsterdam, the Netherlands. Electronic address: d.pegtel@vumc.nl.

Abstract

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.

PMID:
25242326
DOI:
10.1016/j.celrep.2014.08.027
[Indexed for MEDLINE]
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