Journal
RNA BIOLOGY
Volume 16, Issue 5, Pages 696-706Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15476286.2019.1582956
Keywords
Extracellular microRNA; ex-miRNA; kinetics; serum; half-life; microRNA; miRNA
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Funding
- John Fell Fund, University of Oxford [AVD00160]
- Medical Research Council [1371292]
- BBSRC [BB/R021422/1] Funding Source: UKRI
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Multiple studies have described extracellular microRNAs (ex-miRNAs) as being remarkably stable despite the hostile extracellular environment, when stored at 4oC or lower. Here we show that many ex-miRNAs are rapidly degraded when incubated at 37oC in the presence of serum (thereby simulating physiologically relevant conditions). Stability varied widely between miRNAs, with half-lives ranging from similar to 1.5 hours to more than 13 hours. Notably, ex-miRNA half-lives calculated in two different biofluids (murine serum and C2C12 mouse myotube conditioned medium) were highly similar, suggesting that intrinsic sequence properties are a determining factor in miRNA stability. By contrast, ex-miRNAs associated with extracellular vesicles (isolated by size exclusion chromatography) were highly stable. The release of ex-miRNAs from C2C12 myotubes was measured over time, and mathematical modelling revealed miRNA-specific release kinetics. While some ex-miRNAs reached the steady state in cell culture medium within 24 hours, the extracellular level of miR-16 did not reach equilibrium, even after 3 days in culture. These findings are indicative of miRNA-specific release and degradation kinetics with implications for the utility of ex-miRNAs as biomarkers, and for the potential of ex-miRNAs to transfer gene regulatory information between cells.
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