The atypical genesis and bioavailability of the plant-based small RNA MIR2911: Bulking up while breaking down

Abstract

Scope The uptake of dietary plant small RNAs (sRNAs) in consumers remains controversial, which is mainly due to low dietary content in combination with poor fractional absorption. MIR2911, among all the plant sRNAs including microRNAs, has been shown to be one of the most robustly absorbed sRNAs. Here we analyze the unusual abundance and unique genesis of MIR2911 during vegetable processing. Methods and Results Using qRT-PCR, the abundance of MIR2911 increased dramatically in macerated tissues while other microRNAs degraded. The accumulation of MIR2911 correlated with the degradation of the rRNAs, consistent with MIR2911 being derived from the 26S rRNA. Bioinformatic analysis predicts a microRNA-like precursor structure for MIR2911; however, no reciprocal increase in the putative star-strand was noted, and using an Arabidopsis mutation deficient in miRNA processing the accumulation of MIR2911 appeared Dicer independent. MIR2911 was incorporated into the mammalian RNA-induced silencing complex as demonstrated in HEK293T cells, where transfected synthetic MIR2911 modestly suppressed the activity of a cognate luciferase reporter. Conclusion The genesis and increase of MIR2911 post-harvest is atypical, as traditional plant bioactives are less plentiful as vegetables lose freshness. These findings explain the disparity in sera detection between MIR2911 and canonical plant-based miRNAs.

MicroRNAs from plants to animals, do they define a new messenger for communication?

“… Not mentioned RT-qPCR, Bioinformatic, Dual-luciferase reporter assay, Provided insights into the atypical bioavailability of miR2911 and offered engineering strategies for plant-based sRNA therapeutics. [ 147 ] 2015 Orally administered tumor suppressor miRNAs reduced tumor burden in Apc Min/+ mice and were detectable in intestinal tissue. miR34a, miR143, miR145 Synthesized methylated miRNAs Intestinal miR34a was at a detectable level; detection of miR143 and miR145 in mouse intestines were failed.…”

“…Studies supporting biologically relevant uptake of plant-originated miRNAs have focused on miR2911, a honeysuckle-derived miRNA [ 29 , 144 – 147 ]. Honeysuckle is a well-known Chinese herb widely applied in the prevention and control of epidemic diseases.…”

“…Concerning the stability of miR2911, it was proposed to rely on its unique sequence and high GC content. More insightful knowledge of miR2911 was put forward by four independent studies from Yang et al [ 144 – 147 ]. Consistently, Yang reported a significant increase of plant miR2911 in the sera and urine of the honeysuckle decoction-consuming mice [ 144 ].…”

Food‐Derived Xeno‐microRNAs: Influence of Diet and Detectability in Gastrointestinal Tract—Proof‐of‐Principle Study

“…others have provided additional evidence; xenomiRs can be identified in plasma in small retrospective data sets . Novel data suggests atypical behavior of certain miRNAs, for instance miR‐2911 concentration may be increased while other miRNAs become degraded . In one of the latest publications, Huang et al.…”

“…[18] Novel data suggests atypical behavior of certain miRNAs, for instance miR-2911 concentration may be increased while other miRNAs become degraded. [19] In one of the latest publications, Huang et al fed C57BL/six mice with corn and observed no substantial absorption of miRNA in the whole blood or changes in feces miRNA. [20] For the detailed summary we refer to several recent reviews dealing with the progress in the field.…”