A new property of telomerase RNA
MSU chemists have discovered a new protein that protects cells from death
MSU Press Service
A group of Russian scientists led by the Head of the Department of Chemistry of Natural Compounds of the Chemical Faculty of Moscow State University Academician Olga Dontsova discovered a new property of telomerase RNA. It is one of the key components of the cellular enzyme – telomerase. It turned out that telomerase RNA encodes a protein that helps human cells resist stress. The discovery of biochemists will help in the fight against cancer and, perhaps, will bring the creation of effective anti-aging agents closer. The results of the study are published in the journal Nuclear Acids Research (Rubtsova et al., Protein encoded in human telomerase RNA is involved in cell protective pathways).
In recent years, much attention has been paid to research on aging and rejuvenation of the human body. The direction is closely related to the understanding of the mechanism of cell division and the ability of cells to withstand stressful effects caused by various types of radiation, as well as toxic substances or insufficient nutrition of the cell. Most cells are able to divide only a limited number of times. This happens because the end sections of DNA, doubling with each act of division, lose repeating sections – telomeres with each such act. As soon as their number at the end of the DNA becomes critically small, further division becomes impossible, the cell dies.
However, science knows cells capable of almost unlimited division. In relation to the human body, these are embryonic cells, and in the case of a mature organism, stem and cancer cells have this ability. Studies have shown that a special enzyme, telomerase, is active in their nuclei, which completes telomeres at the ends of DNA and in this way indefinitely increases the number of cell division cycles. Until recently, it was believed that telomerase RNA, which is part of telomerase, is non-coding, that is, not involved in protein synthesis in the cell.
A group of scientists from the Faculty of Chemistry of Moscow State University led by Academician of the Russian Academy of Sciences Olga Dontsova in close cooperation with the Research Institute of Physico-Chemical Biology named after A.N. Belozersky Moscow State University managed to show an alternative role of telomerase RNA in human somatic cells. It is present in their cytoplasm in an inactive form and cannot participate in the build-up of telomeric DNA, however, an increase in the content of telomerase RNA in cells affects their stress resistance. It turned out that telomerase RNA is still coding, it encodes protein synthesis (hTERP), which, as shown by immunoblotting, immunofluorescence microscopy and mass spectrometry, is present in cells and consists of 121 amino acids.
Biochemists artificially increased the content of this protein in cells, and then treated them with substances that damage DNA. It turned out that hTERP protects cells from death as a result of apoptosis (that is, disintegration into separate bodies limited by the membrane), which develops in response to DNA damage. Further studies revealed that hTERP is involved in the modulation of so-called autophagy. In this case, the cell digests its part, which has "fallen into disrepair", but survives.
The study of autophagy is of applied importance in the study of the mechanisms of rejuvenation of the body with the help of radical diets: it is believed that cells with limited nutrition utilize their own proteins, in which more and more defects are present over time. Another equally important aspect of the study of autophagy mechanisms concerns its role in tumor formation. It is believed that autophagy reduces the risk of tumor formation in the early stages of this process, but as tumor formation progresses, the same mechanism contributes to the survival of cancer cells in various stressful conditions.
"There are quite a lot of proteins that protect cells from stress," explained one of the authors of the work, associate professor of the Faculty of Chemistry at Moscow State University Maria Rubtsova. – The discovery of a new protein is interesting precisely because it is found in RNA, which was previously considered non-coding. At the same time, it is very actively investigated as a component of telomerase. We discovered that it can have another function if it is located not in the nucleus of a cell, but in its cytoplasm. Studying all the properties of telomerase can bring scientists closer to creating the "elixir of youth" and help in the fight against cancer."
The research was also attended by employees of the Skolkovo Institute of Science and Technology, the V.A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, the M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences and the FSBI FNCC FHM FMBA of Russia.
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