Researchers discover new activities of the enzyme ENDOU

Researchers at the University of Freiburg are discovering new functions of the ENDOU enzyme that are widely distributed, but not widely understood.

The ENDOU enzyme family is found in most organisms, but their actions are nonetheless poorly understood. In humans, it has been linked to cancer.

RNA viruses, such as SARS-CoV2, contain a gene that responds to ENDOU, and this is important for virus reproduction and suppression of the immune response. However, so far only a few details are known about the role of these enzymes.

The research group led by molecular geneticist Dr Wenjing Qi from the University of Freiburg is now adding a little more detail about its role in a study published by the renowned scientific journal “Nature Communications”. . They suggest that the ENDU-2 gene may be responsible for stimulating tumors in the body from a distance.

In addition, the team found a novel, a similar response: Under stress, ENDU-2 can contribute to the organism’s defense and destruction.

The researchers studied the nematode worm C. elegans, which is often used for such genetic studies. More than 60 percent of the genes are similar in worms and humans, including one for ENDOU, known as ENDU-2.

The current theory of tumor development suggests that cancer cells only grow when defects, called mutations, accumulate in their genes. These arise, for example, from radiation, some chemicals, or as you get older. Qi showed back in 2017 that such errors do not have to happen in the cancer cells themselves, but they can occur elsewhere in the body as well.

So cancer is encouraged remotely, so to speak. The researcher suspected that the damaged cells in this case are sending signals to accomplish this, which then reprogram the other figs. Now find the signal for this: ENDU-2.

ENDOU / ENDU-2 not only is selectively released from stressed cells and circulated throughout the body, but can also bind to the RNA (mRNA) messenger of multiple genes at the site original and in the target cells. “

Dr. Wenjing Qi, M.Olecular generator, University of Freiburg

These mRNAs are working copies of genes and are needed as blueprints for the extraction of all proteins and enzymes. What surprised the researcher is that ENDU-2 can perform two different functions under stress: at its original site, it cuts and destroys the mRNA, which reduces metabolism and inhibits on the existing organism from the production of defective new proteins.

At the end, the RNA remains intact, and ENDU-2 helps these cells to survive. For this, however, it must be measured precisely; otherwise, it can cause tumor formation.

One conclusion that can be drawn from this is to say that the worm in particular protects the embryos, i.e. its offspring, at times under great stress.

“In this way, it seems certain that, when the self-healing powers of the organism are not sufficient for both mother and child, it at least ensures the survival of the generation”, comments on the Oll. Dr. Ralf Baumeister, who was also involved in the study and in his department Qi leads a research group.

Freiburg scientists now know that the loss of ENDU-2 can also reprogram cells. These then lose their immortality within a few generations. Next, the team wants to study the conditions that trigger ENDU-2 to differentiate between destruction and protection.

The German Research Foundation is funding the study of Freiburg scientists. In addition, they are collaborating with BIOSS – Center for the Study of Biological Signals and the CIBSS Excellence Cluster – Center for Integrated Biological Indication Studies at the University of Freiburg.