Russian chemists and molecular biologists have found that junk DNA at the ends of chromosomes contains instructions for synthesizing a protein that helps cells not die from stress. Their findings were presented in the journal Nucleic Acids Research.
This protein is interesting in that it is found in RNA, which was previously considered non-coding, one of the "helpers" of telomerase. We discovered that it can have another function if it is not in the cell nucleus, but in its cytoplasm. The study of all the properties of telomerase can bring scientists closer to the creation of the "elixir of youth" and help in the fight against cancer, "said Maria Rubtsova from the Lomonosov Moscow State University, whose words are reported by the university's press service.
The key to immortality
The cells of the embryo and embryonic stem cells are virtually immortal from the point of view of biology - they can live almost indefinitely in an adequate environment, and divide an unlimited number of times. In contrast, cells in the adult body gradually lose their ability to divide after 40-50 division cycles, entering the aging phase, which presumably reduces the chances of developing cancer.
These differences are due to the fact that each division of "adult" cells leads to a reduction in the length of their chromosomes, the ends of which are marked with special repeating segments, the so-called telomeres. When there are too few telomeres, the cell retires and stops participating in the life of the body.
In embryonic and cancer cells, this never happens, since their telomeres are renewed and lengthened with each division thanks to special enzymes, telomerases. The genes responsible for the assembly of these proteins are “turned off” in adult cells, and in recent years, scientists have been actively thinking about whether it is possible to prolong human life by forcibly turning them on or creating an artificial analogue of telomerases.
Rubtsova and her colleagues have long been studying how "natural" telomerases in humans and other mammals work. Recently, they wondered why ordinary cells in the body, where this protein does not work, for some reason synthesize large quantities of one of its assistants, a short RNA molecule called TERC.
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This sequence of about 450 "genetic letters", the biochemist explains, was previously thought to be a common piece of "junk DNA" that telomerase copies and adds to the ends of chromosomes. For this reason, scientists did not pay much attention to the structure of TERC and the possible roles of this fragment of the genome in the life of cells.
Hidden helper
Analyzing the structure of this RNA in human cancer cells, Rubtsova's team noticed that there is a special nucleotide sequence inside it, which usually marks the beginning of a protein molecule. Having found such a curious "piece", the scientists checked whether there are analogues in the cells of other mammals.
It turned out that they were present in the DNA of cats, horses, mice and many other animals, and their structure of this fragment in the genome of each of these animals coincided by about half. This prompted geneticists to believe that inside TERC, not meaningless fragments of ancient genes were preserved, but a completely "living" protein.
They tested this idea by inserting additional copies of this RNA into the DNA of the same cancer cells and making them more actively read such regions. Additionally, the scientists conducted a series of similar experiments on E. coli, in whose genome there are no "classic" chromosomes and telomerases.
It turned out that telomerase RNA was actually responsible for the synthesis of special protein molecules, hTERP, which consisted of only 121 amino acids. Its increased concentration in cancer cells and microbes, as further experiments showed, protected them from various types of cellular stress, saving their lives in case of overheating, lack of food or the appearance of toxins.
The reason for this, as Rubtsova and her colleagues later found out, was that hTERP accelerates the process of "processing" scraps of proteins, RNA and other molecules in lysosomes, the main "incinerators" of the cell. This simultaneously protects them from death and significantly reduces the chances of mutations and the development of cancer.
Further experiments, according to geneticists, will help us understand how telomerase and hTERP interact with each other, and how they can be used to create a kind of "elixir of youth" that is safe from the point of view of oncology.