Hypothetical plant-mammal small RNA communication: Packaging and stoichiometry

The dietary RNA hypothesis suggests that intact foreign RNAs from food can enter the ingesting organism and potentially function, for example, to silence endogenous transcripts. Studies of mammalian uptake have focused mostly on short RNA molecules known as microRNAs (miRNAs), or “xenomiRs” to denote their foreign origin. Enthusiasm about absorption and function of plant xenomiRs has been diminished by negative findings and evidence of contamination and experimental design flaws that account for apparently positive results. Nevertheless, some funding groups, regulatory agencies, and scientists remain interested and invested in the topic. Despite the relative lack of accepted evidence for the hypothesis, this interest is likely to continue into the foreseeable future. It may thus be helpful to identify questions that must be answered if, in the future, mammalian dietary RNA uptake and function are to be proven. Here, I examine packaging and stoichiometry considerations for potential plant-mammal RNA communication.