Reading the Repeats: Cells transcribe telomere DNA

TTAGGG, TTAGGG, TTAGGG, TTAGGG. That’s the piece of the genetic code repeated thousands of times in telomeres, the protective caps on the ends of chromosomes. Now, two groups of scientists have independently discovered that human cells transcribe this seemingly meaningless pattern into RNA molecules, a finding that could have implications for understanding cancer and aging.

Scientists have thought that telomeres merely protect chromosome ends from fraying and other damage, much like the plastic tips on shoelaces. Often, transcribing the genetic information encoded in DNA into matching RNA molecules is the first step in making a protein based on the gene. There seemed to be little reason for cells to transcribe the repetitive DNA in telomeres.

But Maria Blasco and Stefan Schoeftner of the Spanish National Cancer Center in Madrid found telomeric RNA in cells from people, mice, and zebra fish, the team reports online and in an upcoming Nature Cell Biology. The presence of telomeric repeat-containing RNA (TERRA for short) in such distantly related species suggests that telomere transcription is common among vertebrates.

Joachim Lingner of the Swiss Institute for Experimental Cancer Research in Epalinges, Switzerland, and his colleagues first reported the discovery of TERRAs in rat and human cells in the Nov. 2 Science.

Telomeres are thought to play an important role in aging. Each time most cells in a person’s body divide, their telomeres get slightly truncated. This shortening is analogous to a burning fuse. Once telomeres get too short, the cells can no longer divide and soon die.

Immortal cell lines such as tumor cells and stem cells can keep dividing indefinitely because they have an enzyme, called telomerase, that lengthens telomeres.

The discovery of TERRAs raises questions about the molecules’ influence on telomeres and cell immortality. “The evidence that telomere transcription’s going to be a really interesting phenomenon to pursue is extremely high,” comments Woodring E. Wright, a telomere expert at the University of Texas Southwestern Medical Center at Dallas.

The two studies do offer early indications of the functional roles that TERRAs might play. Both teams observed that TERRAs bind to the proteins that package telomeres into a compact form. And in experiments with isolated molecules, Blasco’s team showed that TERRAs inhibit the activity of telomerase, suggesting that TERRAs might impede the lengthening of telomeres within a cell.