A new paper (fulltext pdf) from Chen-Yu Zhang of Nanjing University finds plant microRNA that act on human mRNA inside human cells. Could this be the missing piece, explaining why vitamins, fiber, and macronutrients do not replace fresh fruits and vegetables? Could microRNA be used as orally available therapeutics?

Biological Function

MicroRNA are short (~22 nucleotide) RNA oligamers coded from LncRNA that can bind to mRNA (the RNA that code proteins). A single microRNA can specifically affect a single gene, or target many genes depending on its sequence. When a microRNA binds in an exact match to complementary mRNA, the mRNA is cleaved, generating more microRNA that can again bind mRNA, so microRNA can act like a dominant negative, starting a chain reaction and affect many of the target mRNA. With imperfect hybridization microRNA can still repress the translation of mRNA into protein. MicroRNA are known to be important for the regulation of genes and normal development, and mice engineered to lack certain endogenous microRNA can have major phenotypes similar to those missing protein coding genes.

In the new study a rice microRNA–MIR168a was found in the blood serum of Chinese subjects, and that in mouse it made its way into various tissues including the liver. Not only that, but the microRNA could be functionally significant as it acts on human mRNA including the low-density lipoprotein receptor adapter protein1 (LDLRAP) which in mice decreases LDL removal from mouse plasma.

Missing Piece of Nutrition?

It has long been known that our current understanding of nutrition does not explain the full picture. Supplementation of vitamins, fiber, and minerals does not replace a healthy diet with fresh fruits and vegetables.

It was previously speculated that perhaps we have not identified all of the important vitamins, minerals, and phytochemicals, or that maybe veggies were just acting as fillers and got us to eat less empty carbs and meat.

Maybe miRNA are the missing phytochemicals that make vegetables healthy? Further this would support why the freshness of vegetables is so important–RNA are highly unstable molecules that degrade quickly.

More than a biomarker

At the least this paper is another finding of miRNA acting outside of the original cell, which raises the possibility of administering miRNA–maybe even orally–for disease therapy. It is crucial that we investigate the mechanisms through which this miRNA enters cells, learn if it is important for the nutritionally value of foods, and explore it as an alternative to agonist or inhibitor based pharmaceuticals.