Nobel lecture. Self-splicing and enzymatic activity of an intervening sequence RNA from Tetrahymena.
A living cell requires thousands of different chemical reactions to utilize energy, move, grow, respond to external stimuli and reproduce itself. While these reactions take place spontaneously, they rarely proceed at a rate fast enough for life. Enzymes, biological catalysts found in all cells, greatly accelerate the rates of these chemical reactions and impart on them extraordinary specificity. In 1926, James B. Summer crystallized the enzyme urease and found that it was a protein. Skeptics argued that the enzymatic activity might reside in a trace component of the preparation rather than in the protein (Haldane, 1930), and it took another decade for the generality of Summer's finding to be established. As more and more examples of protein enzymes were found, it began to appear that biological catalysis would be exclusively the realm of proteins. In 1981 and 1982, my research group and I found a case in which RNA, a form of genetic material, was able to cleave and rejoin its own nucleotide linkages. This self-splicing RNA provided the first example of a catalytic active site formed of ribonucleic acid. This lecture gives a personal view of the events that led to our realization of RNA self-splicing and the catalytic potential of RNA. It provides yet another illustration of the circuitous path by which scientific inquiry often proceeds. The decision to expand so many words describing the early experiments means that much of our current knowledge about the system will not be mentioned. For a more comprehensive view of the mechanism and structure of the Tetrahymena self-splicing RNA and RNA catalysis in general, the reader is directed to a number of recent reviews (Cech & Bass, 1986: Cech, 1987, 1988a, 1990; Burke, 1988; Altman, 1989). Possible medical and pharmaceutical implications of RNA catalysis have also been described recently (Cech, 1988b).
Cech
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Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309-0215.
D000818:Animals; D001483:Base Sequence; D007438:Introns; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012313:RNA / Q000235:genetics*; D012326:RNA Splicing; D013768:Tetrahymena / Q000201:enzymology / Q000235:genetics*
D012313:RNA