TERRA Research Opens Doorway for Increasing the Lifespan of Humans

Highlights

• Telomeres transcribe information just like the way DNA does
• The RNA that are transcribed from the telomeres are called TERRA.
• The function of the TERRA is essential to preserving telomeres.

Telomeres are found at the end of DNA strands, they act as a buffer for the DNA strands and aid in

• Protecting the DNA from neucleolytic damage
• Repair
• Fusion with other strands of DNA
• Recombination

Telomeres are short tandem repeats of DNA and in humans they are repeated 3,000 times and extend to about 15,000 base pairs. There is a shortening of the length of telomeres on every DNA replication. Telomeres in DNA Replication

Telomeres aid in protecting the DNA strand from unnecessary recombination and from the DNA strand ends from fusing. However, on every replication, the length of the telomeres are reduced by 20 base pairs. The telomeres continue to reduce in size resulting in a point where the length of the telomeres is reduced to a crucial length.This stops the process of replication and the cell dies through a process called apoptosis. The end of replication and the death of the cell increases as we age and aging cells lead to an aging body.

Telomerase

Telomerase is an enzyme that is responsible for adding the telomere segments TTAGGG to the ends of the chromosome. This enzyme is present in small quantities in somatic cells of normal individuals, which is responsible for the aging of these cells.

Telomerase is present in higher quantities in germ cells as these cells need to sustain their DNA replication and grow into specialized cells.

Telomerase in Cancer Cells

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Telomerase is found in large quantities in cancer cells and this is the reason behind the immortality of these cells and the rapid cell division that takes place.

Causes for the Shortening of Telomeres

1. Obesity: Obese people have a higher risk of reduction in telomere length due to oxidative stress and DNA damage. Studies have shown that there is nearly 8.8 years reduction in lifespan among obese individuals when compared with lean individuals.
2. Smoking: Smoking reduces the length of the telomeres and excessive smoking correlates with telomere damage.
3. Stress: Stress has found to increase damage to telomere length, resulting in shortening.
4. Environmental factors: Certain environmental factors and pollutants could lead to shortening of the telomere length.

TERRA

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The research team led by Maria A. Blasco and colleagues from the Spanish National Cancer Research Centre have found that these tightly packed structures transcribe RNAs that are essential to preserving these repeats. These RNA are called TERRA. The scientists have also identified the region of the genome where these molecules are produced.

Study on Mice

Maria A. Blasco and colleagues studied the TERRA region in mice and found that they were produced in the pair of chromosome 19 and to a lesser extent in chromosome 9.

Study on Humans

The study is published in Nature Communications and details the location of the chromosome from where TERRA are produced. 18 RNA that were earlier thought to be TERRA were studied, however TERRA were produced in the following chromosomes.

• Long arm of chromosome 20 (20q)
• Short arm of chromosome X(Xp)

The researchers verified whether these two regions were significant in the production of TERRA by using the CRISPR-CAS9 system to cut the sites of TERRA production from these 2 chromosomes.

The results showed that the suppression of the chromosome Xp did not have any significant effect on the production of telomeres. However, the suppression of chromosome 20q showed a drastic effect on telomeres.

"Identification of 20q as one of the major locus for human TERRA generation allows us to address the role of TERRA telomere biology," say the authors who continue to study telomeres. The researchers studied the effect of removal of TERRA from cell lines and identified the following

• There was a significant increase in damage to telomere and DNA
• There was an increase in chromosome instability

Dr Basco says "These results are striking because they clearly demonstrate that TERRA play an essential role in cell viability as well as in preserving telomeres; they are just as important to the functioning of telomeres as telomerase or shelterins, the proteins that protect the telomeres."

Highlights of the Study

1. This study provides the first conclusive evidence about the importance of TERRA in protecting telomeres and is the first of its kind studied on any organism.
2. TERRA region production is mapped to the chromosome 20q.
3. The study highlights the importance of TERRA in preserving telomeres. It also associated chromosome 20q to TERRA. This will help in understanding disorders that occur due to alterations in this region of the chromosome.
4. Certain disorders that occur in telomeres have not been associated with telomerase as well as in shelterins. The malformations in TERRA could be studied for these disorders.
5. The effect of TERRA on telomere length can be probed and this could open prospective doorway for studies on aging and increasing the lifespan of humans.
6. The effect of TERRA on the telomere of cancer patients is another area that would benefit medical research.

References:

1. Telomeres, lifestyle, cancer, and aging - (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370421/)
2. What is a telomere? - (http://www.yourgenome.org/facts/what-is-a-telomere)
3. TERRA, the RNAs that protect telomeres - (http://www.eurekalert.org/emb_releases/2016-08/cndi-ttr081616.php)

Source-Medindia