1 Origins and Principles of Translational Control

Proteins occupy a position high on the list of molecules important for life processes. They account for a large fraction of biological macromolecules—about 44% of the human body’s dry weight, for example (Davidson et al. 1973)—they catalyze most of the reactions on which life depends, and they serve numerous structural, transport, regulatory, and other roles in all organisms. Accordingly, a large proportion of the cell’s resources is devoted to translation. The magnitude of this commitment can be appreciated in genetic, biochemical, and cell biological terms. Translation is a sophisticated process requiring extensive biological machinery. One way to gauge the amount of genetic information needed to assemble the protein synthetic machinery is to compile a “parts list” of essential proteins and RNAs. Analyses of the genomes of several microorganisms have converged on similar estimates (Hutchison et al. 1999; Tamas et al. 2002; Kobayashi et al. 2003; Waters et al. 2003). These organisms get by with about 130 genes for components of the translation machinery, including about 90 protein-coding genes (specifying 50–60 ribosomal proteins, about 20 aminoacyl-tRNA synthetases, and 10–15 translation factors) and about 40 genes for ribosomal and transfer RNAs (rRNA and tRNAs). A somewhat larger number of genes are involved in eukaryotes, which have more ribosomal proteins and initiation factors, for example. Discounting genes that are dispensable for growth in the laboratory, it can be calculated that approximately 40% of the genes in a theoretical minimal cellular genome are devoted to the translation apparatus. This heavy...