TY - JOUR
T1 - Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes
AU - Koppers-Lalic, Danijela
AU - Hackenberg, Michael
AU - Bijnsdorp, Irene V.
AU - van Eijndhoven, Monique A J
AU - Sadek, Payman
AU - Sie, Daud
AU - Zini, Nicoletta
AU - Middeldorp, Jaap M.
AU - Ylstra, Bauke
AU - de Menezes, Renee X.
AU - Würdinger, Thomas
AU - Meijer, Gerrit A.
AU - Pegtel, D. Michiel
PY - 2014/9/25
Y1 - 2014/9/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84907415649&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907415649&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2014.08.027
DO - 10.1016/j.celrep.2014.08.027
M3 - Article
C2 - 25242326
AN - SCOPUS:84907415649
VL - 8
SP - 1649
EP - 1658
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 6
ER -