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Title: Anomalous uptake and circulatory characteristics of the plant-based small RNA MIR2911

Author
item YANG, JIAN - Children'S Nutrition Research Center (CNRC)
item HOTZ, TREMEARNE - Bates College
item BROADNAX, LACASSIDY - Children'S Nutrition Research Center (CNRC)
item YARMARKOVICH, MARK - University Of Pennsylvania
item ELBAZ-YOUNES, ISMAIL - Children'S Nutrition Research Center (CNRC)
item HIRSCHI, KENDAL - Children'S Nutrition Research Center (CNRC)

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/9/2016
Publication Date: 6/2/2016
Citation: Yang, J., Hotz, T., Broadnax, L., Yarmarkovich, M., Elbaz-Younes, I., Hirschi, K.D. 2016. Anomalous uptake and circulatory characteristics of the plant-based small RNA MIR2911. Scientific Reports. 6(26834):1-9. doi:10.1038/srep26834.

Interpretive Summary: Nucleic acids, the building blocks of DNA, from plant-based diets may be able to survive digestion and get into a consumers body. If true, this would mean plants can deliver genetic information into the circulatory system to possibly impact health. However, research todate has provided conflicting results on the bioavailability of dietary genetic information. We document here the many common vegetables when part of a standard diet can deliver unique plant-based genetic information to mice. Furthermore, this plant-based small nucleic fed to mice is modified during digestion and uptake to improve sera stability. This work concludes that unique plant-based nucleic acids can be found in consumers. This work provides new mechanistic insights into the dietary delivery of plant-based genetic information to consumers.

Technical 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.