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

doi:10.1016/j.celrep.2014.08.027

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

Istituti Ortopedici Rizzoli

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	1649-1658
Number of pages	10
Journal	Cell Reports
Volume	8
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2014.08.027
Publication status	Published - Sep 25 2014

ASJC Scopus subject areas

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

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Koppers-Lalic, D., Hackenberg, M., Bijnsdorp, I. V., van Eijndhoven, M. A. J., Sadek, P., Sie, D., Zini, N., Middeldorp, J. M., Ylstra, B., de Menezes, R. X., Würdinger, T., Meijer, G. A., & Pegtel, D. M. (2014). Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes. Cell Reports, 8(6), 1649-1658. https://doi.org/10.1016/j.celrep.2014.08.027

Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes. / Koppers-Lalic, Danijela; Hackenberg, Michael; Bijnsdorp, Irene V.; van Eijndhoven, Monique A J; Sadek, Payman; Sie, Daud; Zini, Nicoletta; Middeldorp, Jaap M.; Ylstra, Bauke; de Menezes, Renee X.; Würdinger, Thomas; Meijer, Gerrit A.; Pegtel, D. Michiel.

In: Cell Reports, Vol. 8, No. 6, 25.09.2014, p. 1649-1658.

Research output: Contribution to journal › Article › peer-review

Koppers-Lalic, D, Hackenberg, M, Bijnsdorp, IV, van Eijndhoven, MAJ, Sadek, P, Sie, D, Zini, N, Middeldorp, JM, Ylstra, B, de Menezes, RX, Würdinger, T, Meijer, GA & Pegtel, DM 2014, 'Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes', Cell Reports, vol. 8, no. 6, pp. 1649-1658. https://doi.org/10.1016/j.celrep.2014.08.027

Koppers-Lalic, Danijela ; Hackenberg, Michael ; Bijnsdorp, Irene V. ; van Eijndhoven, Monique A J ; Sadek, Payman ; Sie, Daud ; Zini, Nicoletta ; Middeldorp, Jaap M. ; Ylstra, Bauke ; de Menezes, Renee X. ; Würdinger, Thomas ; Meijer, Gerrit A. ; Pegtel, D. Michiel. / Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes. In: Cell Reports. 2014 ; Vol. 8, No. 6. pp. 1649-1658.

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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.",

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AU - Sadek, Payman

AU - Sie, Daud

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AU - de Menezes, Renee X.

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