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Nobel Laureate Cech discusses discovery and importance of ribozymes

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November 5, 2004

On Thursday afternoon Dr. Thomas Cech, who received the Nobel Prize in Chemistry in 1989, visited Swarthmore to talk about his discovery and characterization of ribozymes. Cech, current president of the Howard Hughes Medical Institute, addressed a large crowd in the science center and discussed the process and end-product of his work.

Professor Amy Vollmer, Biology Department chair, introduced Cech and described him as “a man of great intellect, great compassion…as well as grace and humor.” Cech discussed ribozymes, which are molecules of RNA that are able to catalyze biochemical reactions. Most well-studied molecules that speed up reactions are protein enzymes, and Cech talked about his important discovery of a new class of biomolecules and emphasized the significance of the “pathway” used to come up with the discovering, something that he noted can not often be found in a text book.

Cech gave a brief overview of the Central Dogma of Biology, which states that RNA comes from DNA and that proteins come from RNA; he noted that his view of the central dogma was biased to RNA since it shares with DNA the ability to carry information and with proteins the ability to speed up reactions by lowering their energy of facilitation. Cech then commented on the differences and similarities of DNA and RNA in order to determine why RNA was able to have catalytic ability and noted that since RNA is a single chain, it can fold in many different ways that double-stranded DNA can not. He argued that RNA can fold in a way to have a similar structure to proteins.

Cech then began to talk about his work with Tetrahymena thermophila, a pond organism, and some of his initial discoveries. When looking to find enzymes that help remove introns, or sequences not coding for information in the genetic material, he found that the compound responsible could not be a protein since the reaction was able to proceed without any proteins present. Cech and his colleagues did a great deal of characterization of these newly discovered compounds and found that they closely resembled proteins in terms of kinetics and transition state.

One problem that Cech’s group of researchers encountered was attempting to discover how these RNA molecules folded into very specific shapes like proteins do, especially since proteins have “a lot of chemical diversity” that RNA does not, due to the large variety in amino acids that make up proteins as opposed to the somewhat similar bases that compose RNA. Cech discussed his determining secondary structure and then his use of x-ray crystallography to determine the three dimensional structure.

His initial findings were exciting in that RNA folding ability was determined to be caused by a positive magnesium ion’s neutralizing the RNA’s negative charge; he later found that the ribozyme had a “concave active site” that resembled the binding site on protein enzymes. Cech then discussed a variety of methods used to further characterize these ribozymes, including information from a scientific paper that is coming out today.

Cech ended his talk with a discussion of the “primordial soup,” where the first forms of life developed. At this time, he described, it would make sense that compounds would be needed to carry and replicate information and that RNA could have fit both of these requirements at the same time; Cech argued that there was a good chance that ribozymes were possibly the first molecules available for both information storage and catalysis, which made them so versatile.