How cells feed on RNA

Scientists have discovered that cells can use RNA and its constituent uridine as alternative energy sources to sugar. For better or for worse, as shown by their publication in "Nature Metabolism ".

Each cell contains the genetic material necessary for the activity of the organism. RNA, or ribonucleic acid, is an important molecule for making proteins from the instructions contained in the genes. Any food from a living being, whether plant (fruits and vegetables), animal (meat, fish) or microbial (yeast in bread) contains up to 20% RNA.

Until now, no nutritional value had been attributed to RNA. However, in a study published on May 17, 2023 in the journal Nature Metabolism, the teams of Alexis Jourdain , assistant professor in the Department of Immunobiology at the Faculty of Biology and Medicine (FBM) of the University of Lausanne, and Vamsi Mootha, professor at the Broad Institute of the Massachusetts Institute of Technology (MIT) and Harvard University, showed that RNA has a nutritional value.University of Lausanne, and Vamsi Mootha, professor at the Broad Institute of the Massachusetts Institute of Technology (MIT) and Harvard, have shown that RNA and its constituent, uridine, are used as sugar by the cells, i.e. as energy generator.

The genesis of a find

In the years leading up to his arrival at the University of Lausanne in 2021, Alexis Jourdain worked at the Broad Institute and at Harvard University. It was there that the metabolism specialist focused his investigations on cancer and its unique metabolism.

Glucose is the preferred food of tumor cells, but what happens if they are deprived of this energy source? He then conducted a large-scale genetic screening of samples from nearly 500 tumors, representing some 20 types of cancer.

Unexpectedly, the enzymes responsible for the digestion of RNA and uridine by the cells appeared to be essential for the survival of the cells tested, when sugar is lacking. So I tried adding RNA to my cancer cell culture in the absence of glucose. A few days later, I noticed that the cells had proliferated’, recalls the researcher. Eureka! there was ’nothing left to do’ but to explore this new alternative nutrient pathway and decipher its workings.

An ambivalent source of energy

Once in Lausanne, he focused the work of his research group on energy metabolism and observed that uridine and RNA are assimilated like sugar by the body. This discovery is particularly important in the context of immune and metabolic diseases, as well as cancer. Joan Blanco-Fernández, attracted by the theme, joined the team to carry out his doctorate. Very quickly, completing the history of ’food’ RNA became one of his concerns. He validated previous results in mouse and human immune cells, called macrophages, which are big eaters of pathogens.

I was responsible for the immunometabolic part of the demonstration," says Joan Blanco-Fernández, co-first author of the manuscript. I used small molecules that activate or inhibit this pathway to confirm the results in macrophages.’ The scientists’ work thus reveals two antinomic effects of using RNA as an alternative source of energy. On the one hand, supplying cancer cells is a danger for the body. On the other hand, supplying the immune system is beneficial to defend against attacks.

RNA and uridine on our plate

It had already been established that a diet rich in uridine, the building block of RNA, could lead to diseases such as diabetes and obesity. But the mechanism was still unknown. The exploitation of uridine and RNA as sugar by cells now offers an explanation. And since we ingest large amounts of RNA every day, this discovery could be of interest to nutritionists. oIt is almost impossible to have a diet without any trace of genetic material. However, to restrict sugar intake, one should limit the food in which RNA is abundant, for example fermented foods (bread, beer), certain meats and milk’, advises Alexis Jourdain, last author of the article.

Starving cancers to fight them

Oncologists could also find an interest in it. The idea would be to cut off the food (RNA-rich food) of sugar-loving cancer cells to starve them to death and prevent them from multiplying. At the same time, another American research unit has reached the same conclusions in the context of pancreatic cancer. This is a real opportunity, because this type of tumor was not included in our experiments. Their research complements our own," says Alexis Jourdain. The two studies thus open up a new therapeutic avenue for treating cancers by targeting this mechanism.

In the next few years, Alexis Jourdain and his team in Lausanne hope to be able to identify one or more molecules that inhibit the biological process they have identified. With the support of industrial laboratories, these molecules could be developed into drugs against cancer, but also against metabolic disorders such as obesity, or against diseases of the immune system.