New targets in telomeres?

All our cells contain DNA, in the form of long strings called chromosomes. In the same way that our shoelaces have little plastic caps on their ends that stop them from fraying, our chromosomes are capped by structures, called telomeres, that protect them.

In most of our cells, the telomeres get progressively shorter throughout life. When they get too short, the cells stop dividing. But cancer cells can renew their telomeres, essentially becoming immortal.

Until recently, most scientists thought telomeres were made up of DNA and protein, and this DNA was “silent” – i.e. not actively transcribed to make the “messenger” molecule RNA.

But now researchers in Switzerland have found that telomeres may also contain RNA, copied from the telomeres’ DNA. This revolutionary discovery could have big implications for cancer, as well as other fields such as ageing research.

In a recent paper published in the journal Science, Joachim Lingner and his team studied the makeup of telomeres in minute detail. Using highly sensitive techniques, they found that RNA was being produced from telomeres in cancer cells grown in the lab.

Then the researchers went on to look at whether the telomere RNA, dubbed TERRA, was found in the nucleus of cells in the same places as the telomeres. This result told them that the RNA is probably doing something important at the telomeres, rather than just floating around in the cells.

The scientists found TERRA RNAs in a number of different cell types, showing that their result wasn’t just an artefact from the HeLa cells, but they were really on to something.

The team then went on to look at some of the proteins that are usually found hanging around at telomeres, as well as trying to artificially switch on excessive RNA production from the structures. In conclusion, the researchers believe that the TERRA RNAs may play an important role in organising the telomeres, and making sure they behave properly.

Intriguingly, this bears a close resemblance to another aspect of chromosome behaviour – X inactivation. Women, like all female mammals, have two X chromosomes, while men have an X and a Y.

In order to compensate for this double dosage of X genes, one X chromosome is shut down in all the cells of the female body. RNA produced by the inactive chromosome is a vital part of this process, so could similar mechanisms be at work at telomeres, keeping them under control?

Although it’s at a very early stage, this discovery could change the way we think about telomeres, how they’re made and how they work. And it could point towards new targets for cancer treatments. As always, more work needs to be done, but this is certainly an important development in our understanding of nature’s “shoelaces”.

Kat