A double ring ceremony prepares telomerase RNA to wed its protein partner
Few molecules are more interesting than DNA—except, of course, RNA. After two decades of research, that “other macromolecule” is no longer considered a mere messenger between glamorous DNA and protein-synthesizing machines. We now know that RNA has been leading a secret life, regulating gene expression and partnering with proteins to form catalytic ribonucleoprotein (RNP) complexes. One of those RNPs is telomerase, an enzyme that maintains chromosome integrity.
In a recent study, Stowers Investigator and Howard Hughes Medical Institute Early Career Scientist Peter Baumann, PhD, and his team discovered how the RNA TER1, a component of telomerase, is sculpted to favor interaction with its protein partner: Two ring-like proteins sequentially slip onto unprocessed TER1 RNA and hold it while it is clipped to the optimum size, folded, and capped. That processing is essential; without it TER1 could not engage its protein partner to form the active telomerase RNP.
The finding not only deepens our understanding of RNA biochemistry but also suggests novel pharmaceutical approaches to cancer and diseases of aging. “Cancer cells are exquisitely dependent on telomerase,” says Baumann. “Drugs inhibiting telomerase could be a new class of cancer chemotherapeutics with far fewer side effects than drugs in use.” Currently, biotechnology and pharmaceutical companies are actively seeking clinically useful telomerase inhibitors.
The study was published in the March 26, 2012, issue of Nature.