Nontemplated Nucleotide Additions Distinguish the Small RNA Composition in Cells from Exosomes
Author(s) -
Danijela KoppersLalic,
Michael Hackenberg,
Irene V. Bijnsdorp,
Monique A.J. van Eijndhoven,
Payman Sadek,
Daoud Sie,
Nicoletta Zini,
Jaap M. Middeldorp,
Bauke Ylstra,
Renée X. de Menezes,
Thomas Würdinger,
Gerrit A. Meijer,
D. Michiel Pegtel
Publication year - 2014
Publication title -
cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2014.08.027
Subject(s) - microvesicles , rna , microrna , biology , microbiology and biotechnology , small rna , exosome , extracellular vesicles , non coding rna , computational biology , gene , genetics
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.
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