This is a photograph of subunits of telomerase. Credit: UCLA department of chemistry and biochemistry
Research could lead to new strategies for treating disease. The telomerase enzyme is known to play a significant role in aging and most cancers. Scientists have discovered several major new insights about this enzyme and they are now able to see the complex enzyme’s sub-units in much sharper resolution than ever before.
Telomerase is particularly active in cancer cells, which helps make them immortal and enables cancer to grow and spread. Scientists believe that controlling the length of telomeres in cancer cells could be a way to prevent them from multiplying.
Feigon and her colleagues have been filling in pieces of the telomerase puzzle, using Tetrahymena. Their latest study found that the microorganism’s telomerase is more analogous to human telomerase than previously thought.
Among the new insights the team reported:
~Scientists had thought telomerase contains 8 sub-units: seven proteins and an RNA. But Feigon and her colleagues discovered two additional proteins, Teb2 and Teb3, that increase telomerase’s activity.
~RNA strand interacts with the proteins, but not exactly where it interacted. The new study found that within the enzyme’s “catalytic core,” which is formed by the RNA and its partner proteins TERT and p65, the RNA forms a ring around the donut-shaped TERT protein.
~Scientists previously knew that telomerase contains 3 proteins, p75, p45 and p19, but their structures and functions were poorly understood. The new research identified the proteins’ structures and revealed that they are similar to proteins found at human telomeres.
~The researchers showed that a key protein called p50 interacts with several components of telomerase, including TERT, Teb1 and p75, and this network of interactions has important implications for telomerase’s function.
“It turns out that nearly all, if not all, of the telomerase proteins in Tetrahymena have similar proteins in humans,” Feigon said. “Now we can use our model system to learn more about how telomerase interacts at the telomeres.” Their research could lead to the development of pharmaceuticals that target specific sub-units of telomerase and disrupt interactions between proteins. http://newsroom.ucla.edu/releases/scientists-produce-clearest-ever-images-of-enzyme-that-plays-key-roles-in-aging-cancer
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