Skip to Main Content

Thomas R. Cech

RNA was long thought to function solely as a genetic messenger, as a component of the ribosome, and as a carrier of amino acids. Now, largely because of research done at the University of Colorado, it is just as common to think of RNA participating actively in cellular metabolism. RNA can engage in intramolecular catalysis, including self-splicing, and in some cases, can act as an enzyme. A major goal of the work carried out by Professor Cech and his research group is to understand mechanisms of RNA catalysis at both the chem-ical and the biological levels. The work integrates organic and physical chemistry, enzymology, molecular biology, structural biology, and genetics.

Current efforts focus on the structural biology of large catalytic RNAs, or ribozymes. Crystallographers in the Cech laboratory have grown x-ray diffraction-quality crystals of an active group I ribozyme (247 nt) and solved its struture at modest resolution (5 angstroms). Future work is directed toward obtaining atomic-resolution structures of active group I introns.

The structure and function of telomeres, the natural ends of linear chromosomes, provide a very different area of interest for a portion of Professor Cech’s group. Major biological systems are Euplotes aediculatus, a ciliate that has an unusually large number of linear DNA molecules in its macronucleus, and S. cerevisiae and S. pombe, which are amenable to genetic analysis. Members of the Cech laboratory have cloned and sequenced genes for the catalytic protein subunit of telomerase in Euplotes, S. pombe, human, Tetrahymena and Oxytricha. The active site protein subunits comprise a new class of reverse transcriptases, enzymes previously thought to be restricted to viruses and transposable elements. Long-term goals are to understand the regulation of telomerase by DNA-binding telomere proteins and to understand the nuclear localization and trafficking of telomerase.