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6 How the Group I Intron Works: A Case Study of RNA Structure and Function

James L. Hougland, Joseph A. Piccirilli, Marcello Forconi, Jihee Lee, Daniel Herschlag


In 1968, Leslie Orgel and Francis Crick wrote back-to-back articles in the Journal of Molecular Biology, making the same controversial point: that RNA could, because it could adopt structure (at the time, tRNA was known to adopt its famous “cloverleaf” secondary structure) (Fig. 1), act functionally as a catalyst (Crick 1968; Orgel 1968). Thereby, a solution to the chicken-and-egg problem of the origin of life was proposed. Instead of having to coevolve an information carrier (such as DNA) and a functional macromolecule (such as proteins) to copy information from generation to generation, RNA could have served both roles (Woese 1967; Crick 1968; Orgel 1968). However, the bold suggestions of Orgel and Crick were largely ignored until 1982, when Cech and coworkers discovered the self-splicing activity of the group I intron from Tetrahymena thermophila (Kruger et al. 1982; Cech 1992). The ability of RNA to serve as an information carrier is obvious because it has the same code as DNA and is even used as such in viruses, but RNA’s ability to serve in a capacity analogous to modern-day proteins was not so obvious. Indeed, when this phenomenon was first encountered, it was disbelieved by many and thereafter viewed as mysterious.

The difficulty in appreciating RNA as a functional, catalytic molecule stemmed from both the lack of familiarity with RNA structure (crystal structures were available only for tRNA [Robertus et al. 1974; Suddath et al. 1974; Giege et al. 1977; Hingerty et al. 1978; Sussman et al. 1978; Woo et al....

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