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Abstract
Inconsistent detection of plant-based dietary small RNAs in circulation has thwarted the use of dietary RNA therapeutics. Here we demonstrate mice consuming diets rich in vegetables displayed enhanced serum levels of the plant specific small RNA MIR2911. Differential centrifugation, size-exclusion chromatography, and proteinase K treatment of plant extracts suggest this RNA resides within a proteinase K-sensitive complex. Plant derived MIR2911 was more bioavailable than the synthetic RNA. Furthermore, MIR2911 exhibited unusual digestive stability compared with other synthetic plant microRNAs. The characteristics of circulating MIR2911 were also unusual as it was not associated with exosomes and fractionated as a soluble complex that was insensitive to proteinase K treatment, consistent with MIR2911 being stabilized by modifications conferred by the host. These results indicate that intrinsic stability and plant-based modifications orchestrate consumer uptake of this anomalous plant based small RNA and invite revisiting plant-based microRNA therapeutic approaches.
Highlights
We report here an investigation of the physical state of MIR2911 in both plants and in circulation
Using a modified chow-based diet supplemented with vegetables, we tested whether MIR2911 could be detected from sera of animals consuming these diets
Exposure to dietary MIR2911 can come from a variety of popular vegetables (Table 1)
Summary
We report here an investigation of the physical state of MIR2911 in both plants and in circulation. We measured digestive stability and uptake of the plant-derived MIR2911 in comparison to synthetic MIR2911 and other plant miRNA species. Together the results of the present study demonstrate dietary MIR2911 is packaged and bioavailable from numerous widely consumed vegetables. The MIR2911 complex maybe modified by the host to facilitate circulatory stability. Our results highlight unique plant-based modifications, RNA stability, and host specific alterations as possible prerequisites for detection of a circulating plant-based small RNA and offer a plausible explanation for the inability of numerous groups to detect dietary miRNAs in animal sera
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