Proofreading in Transcription? RNA Fills In Another Missing Piece

Proofreading in Transcription? RNA Fills In Another Missing Piece

The process of proofreading in replication has long been understood, but until recently no such ability had been shown in transcription. To some extent, proofreading was not considered as necessary. An analogy would be the difference between a misprint in a cookbook and misreading the cookbook. In the first case, if the cookbook itself were wrong (DNA), then every attempt to read it would lead to a poor baking attempt. In the latter case, a person who misread the cookbook would make the mistake only once, analogous to making a poor RNA copy one time. Although there could be ramifications to making an incorrect RNA and/or protein, the consequences would be much worse if the DNA itself was wrong.

However, with our current model of the origins of life being based on RNA that had both replicative and catalytic ability, the puzzle was missing a piece. If RNA were the original genetic molecule, then the RNA would have to be replicated faithfully, and some proofreading ability would be necessary. With DNA proofreading, separate proteins do the proofreading, but for the RNA-world hypothesis to hold, RNA would need to have this ability without any protein, which had not evolved yet. Work by Zenkin et al. cited in the bibliography has shown that RNA can indeed catalyze its own proofreading, filling in our missing piece. They demonstrated that a misincor-porated nucleotide could bend back on the previous nucleotide and, in the presence of Mg²⁺ and water, catalyze its own cleavage of the phosphodiester bond, as shown in the figure.