TERRA RNA: A New Telomere Protection Mechanism

Credit: Thomas Ried, NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health

RNA is actually transcribed from your telomere sequences, and new research is suggesting these TERRA RNA sequences play an important role in maintaining chromosomal and telomere integrity

While telomere loss is a primary hallmark of the aging process, there are many factors that contribute to both telomere maintenance and loss. Mice begin life with longer telomeres than humans, but these decline at a much faster rate. While the activity of telomeres and the ability to extend telomeres is clearly a central area of research, understanding what mechanisms help telomeres in a range of cells avoid being damaged or whittled down is also extremely important and should not be understated. 

TERRA and telomeres

For some time telomeres were considered to be relatively inactive 'caps', which effectively held your chromosomes together, but we now know that RNA sequences are actually trancribed from them - in the form of TERRA RNA (telomeric repeat–containing RNA). In a recent article we discussed the discovery that exercise boosts transcription of so called TERRA RNAs, which may play a role in protecting your telomeres against oxidative stress. 

Unravelling the role of TERRA RNA

The latest research at the Telomere and Telomerase Group at the Spanish National Cancer Research Centre (CNIO) has revealed that in humans TERRA RNA is transcribed from two points in your chromosomes: the long arm of chromosome 20 (20q) and at the short arm of chromosome X (Xp). The research team, led by Maria Blasco, tested the validity of these sites by knocking them out with CRISPR technology. Surprisingly, they found that knocking out the Xp site had little effect, but impairing the 20q site on chromosome 20 had disastrous effects on telomere health. 

In mice TERRA is mostly transcribed at chromosome 18, but in humans 20q is the primary TERRA locus. Credit: CNIO

"Identification of 20q as one of the major locus for human TERRA generation allows us to address the role of TERRA telomere biology"

This is the first time any study has definitively shown that TERRA sequences are involved in correct telomere maintenance, and it opens up a whole new avenue of drug development. There are many telomeric disorders that display no apparently alterations in either telomerase or shelterin proteins (another important protein in telomere biology), and this discovery offers fresh insight; suggesting malfunctions in producing TERRA RNA is another route towards telomere dysfunction.

"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"

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