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Researchers at Freiburg University find new functions of this widely disseminated, yet little understood ENDOU enzyme.
The household of ENDOU enzymes is found in most organisms, yet its functions are only poorly known. In humans, it’s been linked with cancer.
RNA viruses, such as SARS-CoV2, contain a gene corresponding to ENDOU, and this is important for virus replication and the suppression of the immune reaction. However, so far just a few particulars of the role of the enzymes are known.
The study group led by the molecular geneticist Dr. Wenjing Qi from the University of Freiburg now contributes some more details to its function in a study released by the renowned scientific journal”Nature Communications”. They suggest that the gene ENDU-2 could be responsible for triggering tumors within the body from a distance.
Moreover, the team discovered a novel, seemingly contradictive answer: Under stress, ENDU-2 can contribute both to the security of the organism and to its own destruction.
The researchers studied the nematode worm C. elegans, which is often used for such genetic analyses. More than 60 percent of the genes are similar in worms and humans, including one for ENDOU, which can be known as ENDU-2.
The present theory of tumor growth suggests that cells only become cancer cells when errors, known as mutations, accumulate in their genes. These arise, for example, from radiation, certain chemicals, or through aging. Qi revealed back in 2017 that such mistakes do not have to occur in the cancer cells themselves, but they can also arise elsewhere in the body.
Cancer is consequently triggered remotely, so to speak. The researcher guessed that the damaged cells in this case send signals to achieve this, which then reprogram the other tissues. They now discovered the sign for this: ENDU-2.
These mRNAs are the working copies of enzymes and are needed as blueprints for the production of proteins and enzymes. What surprised the researcher was that ENDU-2 can perform two different functions under stress: at the site of origin, it cuts and destroys the mRNA, which reduces metabolism and prevents the stressed organism from making faulty new proteins.
For this, however, it must be dosed precisely; differently, it can cause tumor formation.
One conclusion that may be drawn from this could be the pig specifically protects the embryos, i.e. its offspring, in times of great stress.
“In this manner, it sounds guaranteed that whenever the organism’s self-healing powers aren’t sufficient for mom and child, it ensures that the survival of the progeny”, speculates Prof. Dr. Ralf Baumeister, who was also involved in the analysis and in whose division Qi leads a study group.
The Freiburg scientists now know that the loss of ENDU-2 can also reprogram stem cells. These then lose their immortality within a few generations. Next, the team wants to explore which conditions cause ENDU-2 to distinguish between destruction and protection.
The German Research Foundation is funding the Freiburg scientists’ research. In addition, they’re cooperating with BIOSS – Centre for Biological Signalling Studies and the Excellence Cluster CIBSS – Centre for Integrative Biological Signalling Research in the University of Freiburg.
