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11 Structure and Mechanism of the Large Catalytic RNAs: Group I and Group II Introns and Ribonuclease P

Thomas R. Cech


Living cells require thousands of different chemical reactions to grow, store energy, move, respond to external stimuli, and reproduce. These reactions may take place spontaneously, but they rarely occur at a rate fast enough to support life. Biological catalysts accelerate these reactions, often by a factor of a billion or even a trillion, and also impart on them exquisite specificity. Biological catalysis is mostly the realm of protein enzymes, at least in modern cells. During the past decade, however, we have come to see that proteins do not have a monopoly on biological catalysis. Some RNA molecules are able to fold up to form active sites that catalyze chemical reactions, perhaps including a key reaction of protein synthesis. Furthermore, there is much speculation that RNA catalysis may have made an essential contribution to the establishment of self-replication and information-directed protein synthesis in early evolution.

The purpose of this chapter is to describe what we know and what we would like to know about some of these catalytic RNAs, or “ribozymes” (Kruger et al. 1982). The specific questions are those of structure (How do these RNAs fold to form an active site?) and mechanism (What chemical reactions occur and how are they catalyzed?). The decision to cover the group I and group II introns and the catalytic RNA subunit of RNase P in a single review is justifiable on two grounds. First, these are all large ribozymes compared, for example, to the hammerhead (see Pan et al., this volume). Although size...

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