Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics
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 physiol...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Taylor and Francis
2019
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| _version_ | 1826274781507354624 |
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| author | Coenen-Stass, A Pauwels, M Hanson, B Martin Perez, C Conceição, M Wood, M Mäger, I Roberts, T |
| author_facet | Coenen-Stass, A Pauwels, M Hanson, B Martin Perez, C Conceição, M Wood, M Mäger, I Roberts, T |
| author_sort | Coenen-Stass, A |
| collection | OXFORD |
| description | 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 ~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. |
| first_indexed | 2024-03-06T22:48:39Z |
| format | Journal article |
| id | oxford-uuid:5e0f4bc3-0fd3-41c2-be20-d7828f93050c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:48:39Z |
| publishDate | 2019 |
| publisher | Taylor and Francis |
| record_format | dspace |
| spelling | oxford-uuid:5e0f4bc3-0fd3-41c2-be20-d7828f93050c2022-03-26T17:38:14ZExtracellular microRNAs exhibit sequence-dependent stability and cellular release kineticsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5e0f4bc3-0fd3-41c2-be20-d7828f93050cEnglishSymplectic Elements at OxfordTaylor and Francis2019Coenen-Stass, APauwels, MHanson, BMartin Perez, CConceição, MWood, MMäger, IRoberts, TMultiple 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 ~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. |
| spellingShingle | Coenen-Stass, A Pauwels, M Hanson, B Martin Perez, C Conceição, M Wood, M Mäger, I Roberts, T Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics |
| title | Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics |
| title_full | Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics |
| title_fullStr | Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics |
| title_full_unstemmed | Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics |
| title_short | Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics |
| title_sort | extracellular micrornas exhibit sequence dependent stability and cellular release kinetics |
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