Unraveling the Mechanism of how TERRA accumulates at Telomeres in order to protect cells from premature aging

Scientists have identified the mechanism that prevents cells from prematurely aging

It was not clear how TERRA reached the tip of chromosomes, and remained there. Lingner says that the telomere only makes up a small part of chromosomal RNA, and the question then is \”how does this RNA get to its destination?\” Marianna Feretzaki, a postdoctoral fellow at EPFL, and Lumir Krejci, a professor at Masaryk University, set out to answer this question. They studied the mechanisms by which TERRA accumulates in telomeres as well as proteins involved in the process. The findings were published in the journal * Nature*.

**Finding home**

The researchers discovered that a small stretch of RNA was crucial for bringing TERRA to telomeres. TERRA reaches chromosome tips, and several proteins control its association with telomeres. Lingner says that RAD51 is one of these proteins.

RAD51, a well-known DNA repair enzyme, is responsible for the repair of damaged DNA molecules. The protein appears to also help TERRA adhere to telomeric RNA to form a \”RNA-DNA-hybrid molecule\”. Scientists believed that this reaction, which results in the formation of three-stranded nucleic acids, occurred mainly during DNA repair. The new study shows it can happen at chromosomes ends when TERRA binds with telomeres. Lingner states that \”this is a paradigm-shifting\” study.

Researchers also discovered that short telomeres recruited TERRA molecules much more effectively than long telomeres. The researchers believe that although the mechanism is not clear, when telomeres become too short due to DNA damage, or because the cells have divided too often, they attract TERRA molecules. This recruitment is mediated through RAD51 which promotes elongation of telomeres and their repair. Lingner explains that \”TERRA, RAD51 and RAD52 help prevent accidental loss or a shortening of telomeres.\” This is an important function.

Researchers at EPFL have uncovered how molecules that accumulate on the tips of chromosomes play a crucial role in protecting our DNA. Researchers at EPFL have now figured out how these molecules target specific sections of the chromosomes. This discovery could help better understand processes that regulate cell life in cancer and aging.

Telomeres, like the aglet on a shoelace, form protective caps that protect the ends of the chromosomes. As cells divide, the telomeres get shorter and less protective. When telomeres become too short, cells stop dividing. Telomere malfunction and shortening have been associated with cell aging, age-related diseases and cancer.

Scientists know that RNA species named TERRA regulate the length and functionality of telomeres. TERRA was discovered in 2007 by Claus Azzalin, a postdoc in Professor Joachim Lingner’s team. It belongs to a group of molecules known as noncoding RNAs. These molecules are not translated into protein but act as structural components in chromosomes. TERRA is accumulated at chromosomes ends and signals that telomeres need to be elongated.


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