Diet and genes: The cross-kingdom regulation

In the last 15 years, important advances in biological research led to the discovery of a new class of molecules, the micro RNAs (miRNAs), that are strongly involved in gene regulation. miRNAs are a class of 19-24 nucleotide long non-coding RNAs that mediate the post-transcriptional silencing of an estimated 30% of protein-coding genes in mammals by pairing with complementary sites in the 3′ untranslated regions (UTRs) of target genes. miRNAs are widely expressed in animals and plants. They modulate various critical biological processes, including differentiation, apoptosis, proliferation, the immune response, and the maintenance of cell and tissue identity. Dysregulation of miRNAs has been linked to cancer (Ref.) and other diseases. Numerous reports have shown that unique expression patterns of circulating miRNAs reflect various physiological and pathological conditions. Blood serum miRNA expression profiles show a great potential to serve as a novel class of biomarkers for the diagnosis of cancer and other diseases.

A paper by Lin Zhang et al. (Cell Research (2012) 22:107-126.) shows evidence of cross-kingdom regulation by microRNA. The researchers showed that a specific exogenous plant miRNA (MIR168a) from food intake can regulate plasma LDL-cholesterol level, implicating a physiological relevance of food-derived plant miRNAs.
Upon investigation of the global miRNA expression profile in human serum, the researchers found that exogenous plant miRNAs were consistently present in the serum of healthy Chinese men and women whose main diet was rice. Food-derived mature plant miRNAs can be detected even after cooking the food and resistant to enzymatic digest in GI. This implies that exogenous plant mature miRNAs in food can pass through the GI tract and be transferred into the blood-stream and tissues. intestinal epithelial take up plant miRNAs in food, then pack them into Microvesicles (MVs) and release the miRNA-containing MVs into the circulatory system. These MVs secreted from intestinal epithelial cells would then deliver exogenous plant miRNAs into other organs and regulate the function of recipient cells.

These findings significantly extend the understanding of the role of miRNAs. With their robust stability and highly conserved sequences, secretory miRNAs can act not only in a cross-species, but also a cross-kingdom fashion. In this sense, miRNAs may represent a novel class of universal modulators that play an important role in mediating animal-plant interactions at the molecular level. Like vitamins, minerals and other essential nutrients derived from food sources, plant miRNAs may serve as a novel functional component of food and make a critical contribution to maintaining and shaping animal body structure and function. Extending from this concept, the intake of certain plant miRNAs generation after generation through a particular food source may leave an imprint on the genetic map of the human race. In conclusion, the discovery of plant miRNAs and their roles in the biology of mammalian cells and animal organs represents a clear evidence of cross-kingdom transfer of functionally active miRNAs and opens a new avenue to explore miRNA-mediated animal-plant interactions.