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

Danijela Koppers-Lalic, Michael Hackenberg, Irene V. Bijnsdorp, Monique A J van Eijndhoven, Payman Sadek, Daud Sie, Nicoletta Zini, Jaap M. Middeldorp, Bauke Ylstra, Renee X. de Menezes, Thomas Würdinger, Gerrit A. Meijer, D. Michiel Pegtel

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1649-1658
Number of pages10
JournalCell Reports
Volume8
Issue number6
DOIs
Publication statusPublished - Sep 25 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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