title: Anomalous uptake and circulatory characteristics of the plant-based small RNA MIR2911.
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.
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, TX 77030, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Bates College, 2 Andrews Rd, Lewiston, ME 04240, USA.
authors.forename: Tremearne
authors.initials: T
authors.lastname: Hotz
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, TX 77030, USA.
authors.forename: LaCassidy
authors.initials: L
authors.lastname: Broadnax
authors.affiliation: Cancer Biology, University of Pennsylvania, 3501 Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Yarmarkovich
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, TX 77030, USA.
authors.forename: Ismail
authors.initials: I
authors.lastname: Elbaz-Younes
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, TX 77030, USA.|Vegetable and Fruit Improvement Center, Texas A&M University, College Station, TX 77845, USA.
authors.forename: Kendal D
authors.initials: KD
authors.lastname: Hirschi
mesh_terms: D000821:Animal Feed; D000818:Animals; D001682:Biological Availability; D001937:Brassica / Q000737:chemistry; D004063:Digestion; D019286:Endopeptidase K / Q000378:metabolism; D055354:Exosomes; D019684:Magnoliopsida / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000097:blood* / Q000493:pharmacokinetics*; D053758:Nanoparticles; D020871:RNA Stability
chemical_list: D035683:MicroRNAs; D019286:Endopeptidase K