Télomères des chromosomes

Unexpected role found for DNA caps on chromosomes.

Heidi Ledford

Telomeres, the stretches of repetitive DNA that cap chromosome ends, have long been thought to be solely for protecting the ‘important' DNA behind them from wear and tear. Now researchers have discovered that these caps are doing something more - they're coding for RNA.

"This really is a breakthrough," says Laure Sabatier, a molecular biologist at the French Atomic Energy Commission in Fontenay-aux-Roses, who was not associated with the study.

Each time chromosomes are replicated, some of the DNA at the ends is lost. Telomeres buffer against the removal of important genetic information by sacrificing their own length rather than allowing deletions to creep into the portions of DNA that code for RNA and protein.

That means that as cells age, telomeres gradually become shorter. Some cancer cells achieve immortality by maintaining long telomeres, and the proteins responsible for achieving this are potential targets for anti-cancer therapies.

The DNA that makes up telomeres does not contain recognizable genes. If anything, they have a gene-silencing effect - the structure of telomeres can interfere with nearby stretches of DNA, stopping them from producing RNA. No one expected telomeres to serve as a DNA template for the synthesis of RNA, says Sabatier.

Serendipity

The discovery was made by accident. Joachim Lingner, of the Swiss Institute of Experimental Cancer Research in Epalinges and the Swiss Federal Institute of Technology in Lausanne, and his colleagues were studying a protein involved in degrading RNA. They noticed that the protein was associated with telomeres. "We reasoned that if you have this entire machinery sitting at the telomere, perhaps there is RNA there," says Lingner.

From there it was a simple assay to see whether RNA corresponding to the telomere sequence was present. Lingner and his co-workers found the RNA, which remained clustered primarily near the telomeres. The results are published this week in Science.

Whether the discovery will provide new avenues for cancer therapies remains unclear, Lingner notes. It isn't yet known what the RNA is doing - it isn't expected to code for protein, but Lingner speculates that it may have a role in regulating telomere length. The researchers found that if they deleted RNA-degrading proteins located nearby, more of the telomere RNA accumulated around the telomeres. When this occurred, the telomeres became unstable and were more likely to fragment.

"We see a high rate of telomere loss at the same time as the RNA levels go up at the telomere," says Lingner, "but it is important to know whether it is the RNA that directly creates this problem".

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