Small RNA Sequencing in Cells and Exosomes Identifies eQTLs and 14q32 as a Region of Active Export

Abstract Exosomes are small extracellular vesicles that carry heterogeneous cargo, including RNA, between cells. Increasing evidence suggests that exosomes are important mediators of intercellular communication and biomarkers of disease. Despite this, the variability of exosomal RNA between individu...

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Published in:G3 : genes - genomes - genetics Vol. 7; no. 1; pp. 31 - 39
Main Authors: Tsang, Emily K, Abell, Nathan S, Li, Xin, Anaya, Vanessa, Karczewski, Konrad J, Knowles, David A, Sierra, Raymond G, Smith, Kevin S, Montgomery, Stephen B
Format: Journal Article
Language:English
Published: England Oxford University Press 01.01.2017
Genetics Society of America
Subjects:
BASIC BIOLOGICAL SCIENCES
Cell Line
Chromosomes, Human, Pair 14 - genetics
Exosomes - genetics
extracellular vesicles
Gene Expression Regulation
gene regulation
High-Throughput Nucleotide Sequencing
Humans
Investigations
Lymphocyte Activation - genetics
MicroRNAs
MicroRNAs - genetics
miRNA
piRNA
Quantitative Trait Loci - genetics
RNA, Small Interfering - genetics
Sequence Analysis, RNA
miRNA
extracellular vesicles
gene regulation
piRNA
ISSN:2160-1836, 2160-1836
Online Access:Get full text
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Summary:Abstract Exosomes are small extracellular vesicles that carry heterogeneous cargo, including RNA, between cells. Increasing evidence suggests that exosomes are important mediators of intercellular communication and biomarkers of disease. Despite this, the variability of exosomal RNA between individuals has not been well quantified. To assess this variability, we sequenced the small RNA of cells and exosomes from a 17-member family. Across individuals, we show that selective export of miRNAs occurs not only at the level of specific transcripts, but that a cluster of 74 mature miRNAs on chromosome 14q32 is massively exported in exosomes while mostly absent from cells. We also observe more interindividual variability between exosomal samples than between cellular ones and identify four miRNA expression quantitative trait loci shared between cells and exosomes. Our findings indicate that genomically colocated miRNAs can be exported together and highlight the variability in exosomal miRNA levels between individuals as relevant for exosome use as diagnostics.
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USDOE
AC02-76SF00515
ISSN:2160-1836
2160-1836
DOI:10.1534/g3.116.036137