When we eat, the leaves and fruits are dismantled by our teeth and pulverized in the gut. The proteins, carbohydrates and lipids released by this process enter the body and are distributed everywhere along the bloodstream, adding to the body. But that may not be the whole story – Professor Zhang Chenyu of the School of Life Sciences at Nanjing University has discovered that there are small molecules in plants that also enter the body and may backfire, controlling the body’s genetic activity and affecting the body in a more proactive way. These arrogant small molecules are tiny ribonucleic acids (micro RNA, miRNA). The study was published in Cell Research.
As the name implies, microRNAs are small, only 19-24 nucleotides; they are not exclusive to plants, but also to animals. Whether plant or animal, they are very important for cell growth and metabolism. But the academic community has always believed that the self-produced micro RNA is only for their own use; it never occurred to them that the plant’s may also survive in the human body and even perform killer duties. Zhang Chenyu wondered, “Why not?
Those hardy micro RNAs
To test their suspicions, Zhang Chenyu’s team first found a group of people and drew their blood to look for traces of plant micro RNAs inside. It turns out that human blood harbors at least 40 plant-specific micro RNAs! There are thousands of micro RNAs in plants, and according to previous knowledge, these micro RNAs should not be able to withstand the digestive tract, but now Zhang Chenyu’s experiment proves that a very small number of them can survive, which is an amazing discovery!
Why these few tiny RNAs survived, Zhang Chenyu said he didn’t know. However, he found that among the more than 40 kinds of micro RNAs that survived, two numbered MIR156a and MIR168a were particularly hardy, with concentrations in the same order of magnitude as the concentration of micro RNAs in the human body itself. The two micro RNAs are the most abundant in rice and cabbage (the most abundant in raw rice, with nearly 40% left in cooked rice). In addition to rice, MIR156a is also abundant in wheat, and unlike the results of previous studies, MIR156a was missing from Zhang Chenyu’s team’s assay.
Well, since plant-derived microRNAs have been found in humans, do they indeed come from the diet? And what effect could they have in animals? Zhang Chenyu’s team took MIR168a, which is abundant in rice, and analyzed it.
Rats love rice …… experiment was done with mice.
Micro RNA cross-species “murder”
By feeding raw rice to mice, the scientists found that their blood and liver concentrations of MIR168a did increase as a result of the increased MIR168a in their diet. What other effects would the increase have?
To predict what kind of physiological results an increase in plant microRNAs can cause, one has to understand how microRNAs work. In a cell, DNA is like a blueprint full of genetic information that is “copied” at the right time into messenger RNA (mRNA), which directs protein synthesis. MicroRNAs, like killers, are very specific in finding the messenger RNAs they want to murder so that they cannot continue to make proteins. Of course, microRNAs don’t look at photos to find their targets, but at how well the messenger RNAs match them, and if there are certain fragments of the messenger RNAs that they happen to bind to, those messenger RNAs are considered to be the damn targets. So who are the murder targets of MIR168a from plants in animals?
After sequence comparison, scientists speculate that it does have a messenger RNA target in animals, and this messenger RNA directs the synthesis of the protein that “kidnaps” LDL, and this kidnapper is mainly located in the liver. In other words, MIR168a, a tiny RNA, is specialized in dealing with kidnappers, and if MIR168a is elevated, there will be fewer kidnappers in the liver, and LDL will not be kidnapped, and the concentration in the blood will slowly accumulate and become higher.
Sure enough, they found that after eating rice, the MIR168a in the mice quickly rose, and after 3 days, the LDL cholesterol in the blood also became more. All this verified Zhang Chenyu’s conjecture and at the same time made the scientific community incredulous: the tiny RNA from plants is actually a super killer that can perform murderous tasks across species!
A side of water feeds a side of people
But if plants are so powerful that they can regulate our genes if we eat them, should we stay away from them? Zhang Chenyu thinks this worry is unnecessary: “Do not be afraid, this phenomenon to be established in the human body, further proof is needed. Moreover, even if such regulatory pathways are present, we have been regulated throughout billions of years of evolution, and the body has long since reached equilibrium.”
He noted, however, that his study may provide a scientific footnote to the old Chinese saying, “One side of the soil feeds one side of the people,” because if the results obtained in the mouse experiments can really be extrapolated to humans, it may explain why Easterners get diabetes even though they are less fat compared to Westerners — because Easterners eat mainly rice and Westerners eat mainly bread, “so eating rice and eating noodles may be different,” Zhang Chenyu said. Of course, there are many factors that diet can influence the body, and the regulation of tiny RNAs is just a guess. (We can all express our own opinions about the differences between Easterners and Westerners.)
Ultimately, experiments on organisms are still at the stage of mice, and it’s still a bit bold to extend the conclusions of mice directly to people. And most importantly, what is the mechanism through which the regulation of microRNAs across the “boundary” actually occurs? Only by clarifying the mechanism can we better explain the phenomenon and guide future applications. This is a difficult problem in front of Chen-Yu Zhang.
Mechanism research is still waiting for more exciting experiments
Based on previous research, Zhang Chenyu knew that small vesicles in the blood can load up micro RNA and transport it to other parts of the body, so he guessed that small intestinal villi might also swallow in micro RNA from plants that are free in the vicinity, wrap it into small vesicles, and then spit it out into the blood vessels. The vesicles then travel downstream, and if they travel to the liver, these vesicles may be absorbed by the liver cells, and the tiny RNA is released, whereupon it binds to its target messenger RNA, leaving fewer LDL abductors and causing the bad cholesterol in the blood to rise.
This process sounds as exciting as a crime solving story! Yet it is not easy to prove – think about it, how is it possible to see this process with your own eyes? Up to now, scientists have not been able to confirm this conjecture in intact organisms either, but can only say that efforts have been made in this direction.
Zhang Chenyu’s team simulated the above scenario using human cells. They first “fed” a large amount of synthetic MIR168a microRNA to human epithelial cells (small intestinal villi are a type of epithelial cells) cultured in vitro (i.e., in a flat dish). The vesicles secreted by these epithelial cells are then collected. These were then transferred to liver cells cultured in a separate dish. Then they found that the amount of kidnappers that MIR168a was trying to murder was really reduced in the liver cells.
Such cellular experiments did prove that Zhang Chenyu’s conjectured mechanism was feasible, however it was after all done between two cultured cells separated from each other, not at the level of the organism, so the mechanism was only tentatively verified and far from conclusive. More exciting experiments are yet to come to conclusively state the mechanism of plant microRNA action on human body. Since Zhang Chenyu’s study overturned common knowledge and only one of the dozens of plant microRNAs that survive in humans, MIR168a, was found to act on animals, it was thought that his results might be coincidental. Petr Svoboda, from the Institute of Molecular Genetics in the Czech Republic, believes that the amount of plant microRNAs detected in the human body in C.Y. Zhang’s experiments was very small, and it is doubtful whether this concentration of microRNAs can really have an effect on humans. It is doubtful.
Although the concentration of MIR168a is less than the total amount of microRNA in human body, it is comparable to the concentration of some microRNA in human body, which is enough to function.
In any case, there are many factors in plants that can work on animals. This study simply suggests that such a pathway may still exist in plants to regulate the body of animals. What can be believed is that on the evolutionary scale, although animals and plants have shared a short period of time together, and in taxonomy, although they are indeed grouped at opposite ends of the spectrum, animals and plants have been influencing, penetrating, and even transmitting information to each other in various ways. We are racking our brains to try to penetrate the inextricable links between these distances.