Robust profiling of microRNAs and isomiRs in human plasma exosomes across 46 individuals

Tommy A Karlsen,Tommy F Aae,Jan E Brinchmann

doi:10.1038/s41598-019-56593-7

Tommy A Karlsen, Tommy F Aae + Show 1 more

Open Access

https://doi.org/10.1038/s41598-019-56593-7

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Abstract

microRNAs (miRNAs) are small double stranded RNA molecules consisting of two complementary strands called the 5p and 3p arms. Following imprecise processing and/or addition of nucleotides at the ends, miRNA biogenesis can give rise to variants called isomiRs. Exosomes are small vesicles released by cells. They have attracted attention due to their potential use in biomarker development because of their content of biomolecules, including miRNAs and isomiRs. Exosomes are found in body fluids such as plasma. In this study we used next generation sequencing to investigate the distribution of 5p and 3p arms of both miRNAs and isomiRs in plasma exosomes from 46 individuals. Among the canonical miRNAs there was similar prevalence between 5p and 3p miRNAs. Most of the miRNAs had isomiRs, and in approximately half of the cases an isomiR was more abundant than the corresponding canonical miRNA. Most of the isomiRs were generated from 5p miRNAs. There were very small differences in the concentration of canonical miRNA and isomiR sequences between donors, suggesting tight control of isomiR generation and sorting into exosomes. IsomiRs are abundant in plasma exosomes and should be included in analysis when plasma exosomal miRNAs are investigated as potential biomarkers for disease development.

Highlights

MicroRNAs are small double stranded RNA molecules consisting of two complementary strands called the 5p and 3p arms
The data in this study presents the distribution and abundance of canonical 5p and 3p arms and canonical miRNAs and isomiR sequences in plasma-derived exosomes
One possibility is that miRNAs are transported by RNA-binding proteins (RBP) from the RNA-induced silencing complex (RISC) to multivesicular bodies (MVB) for exosome loading

Summary

Introduction

MicroRNAs (miRNAs) are small double stranded RNA molecules consisting of two complementary strands called the 5p and 3p arms. Exosomes are small vesicles released by cells They have attracted attention due to their potential use in biomarker development because of their content of biomolecules, including miRNAs and isomiRs. Exosomes are found in body fluids such as plasma. Monitoring miRNA levels in different cell types, tissues and body fluids, such as plasma, serum and urine has attracted attention because of their potential use as biomarkers for disease development[3]. During their multistep biogenesis miRNAs are first transcribed as primary transcripts (pri-miRNA). Substitution of nt within the seed will give rise to new seed sequences while changes at the 3′-end can affect the stability of the isomiR2

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