Isn't it time to lengthen telomeres?
Scientists have found out how cells protect themselves from cancer and aging
Czech and Swiss biologists have established mechanisms that allow cells to repair telomeres – molecules that protect DNA from damage. The results of the study are published in the journal Nature (Feretzaki et al., RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops).
Just as the tip on a shoelace prevents it from wearing off, sections of DNA called telomeres form protective caps at the ends of chromosomes. With age, as cells divide, telomeres shorten, which reduces the effectiveness of their protective function. When the telomeres become too short, the cell stops dividing.
This is usually associated with aging processes and age-related diseases, a similar pattern is observed in oncopathology.
Researchers from the Federal Polytechnic School in Lausanne (EPFL) and Masaryk University in Brno found out that an RNA molecule called TERRA helps telomeres take their strictly defined place.
"Telomeres make up only a tiny part of the entire chromosomal DNA, so the question is how this RNA finds its home," the EPFL press release quotes the head of the study, Professor Joachim Lingner (Joachim Lingner).
To answer this question, the authors analyzed the mechanism by which TERRA accumulates on telomeres, and also found out which proteins are involved in this process.
TERRA was discovered in 2007 in Lingner's laboratory. It belongs to the class of non-coding RNAs that are not translated into proteins, but function as structural components of chromosomes. Scientists knew from previous studies that TERRA at the ends of chromosomes signals that telomeres should be lengthened or restored, but how it turns out there was still unknown.
Visualizing TERRA molecules under a microscope, the researchers found that a specific RNA site is crucial for delivering it to telomeres, and when the molecule reaches the end of the chromosome, its connection to telomeres is regulated by the RAD51 protein, a well–known enzyme that is involved in repairing damaged DNA molecules.
It turned out that this protein also helps TERRA to attach to telomeric DNA, forming a so-called "hybrid RNA-DNA molecule". Before that, scientists thought that such a reaction, leading to the formation of a three-stranded structure of nucleic acid, mainly takes place during DNA repair. A new study has shown that it also occurs at the ends of chromosomes when TERRA binds to telomeres.
"It's a paradigm shift," Lingner says.
The researchers also found that short telomeres attract TERRA much more effectively than long ones. Although the mechanism of this phenomenon is still unclear, the researchers suggest that when telomeres become too short – either due to DNA damage or because the cell divides too many times - they attract TERRA molecules. According to scientists, this is a kind of mechanism for protecting cells from premature aging.
"TERRA and RAD51 help prevent accidental loss or shortening of telomeres. This is an important function," the scientist notes.
The authors reproduced in test tubes the mechanism they discovered during observations on living cells. In the next stage of research, they plan to find out whether the RAD51 protein affects the binding of other non-coding RNAs to chromosomes, and to understand the functions that this connection provides.
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