Getting down to RNA
doi:10.1038/nindia.2009.267 Published online 5 August 2009
Researchers have long known that ends of chromosomes can harbour quadruplexes, a type of roughly cubical structure made of short stretches of DNA. Now, an Indian research team has found quadruplex forming potential at the RNA level1.
Insights into such structures might provide a lead in extending the knowledge generated for the DNA quadruplex to the RNA level. In addition, the findings could help churn out drugs that may regulate gene expression leading to medicinal benefits such as anti-cancer activity.
Growing evidence suggests that human genes contain close to 376,000 quadruplex-forming sequences. DNA quadruplexes form in telomeres (the ends of chromosomes like the tips of shoe laces). In telomeres, such structures have been shown to inhibit the activity of telomerase, an enzyme aiding in unbridled growth of cancer cells.
The researchers took DNA and RNA from human telomeres. They saw that the RNA quadruplex adopts a parallel conformation and displays remarkably high thermal stability as compared to its DNA counterpart. Both telomeric RNA and DNA were seen to possess similar recognition ability for a specific type (TMPyP4) of molecules.
The findings are significant as telomerase can't extend quadruplex-containing telomeres, failing to recognize them as a substrate. It only copies linear strands of DNA. The resulting loss of telomerase activity causes cancer cells to lose the ability to divide, which leads to cell death.
- Arora, A. et al. Differential Biophysical Behavior of Human Telomeric RNA and DNA Quadruplex. J. Phys. Chem. B. 113, 10515-10520 (2009) | Article |