1 Origins and Principles of Translational Control

Abstract

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 both genetic and biochemical terms.

Translation is a sophisticated process requiring extensive biological machinery. One way to estimate the minimal amount of genetic information needed to assemble the protein synthetic machinery would be to compile a “parts list” of essential proteins and RNAs and add up their sizes. However, this approach entails several questionable assumptions about the identity of the essential components and their minimal sizes. An alternative approach is to examine the genomes of simple living organisms. The smallest known cellular genome, that of the parasitic bacterium Mycoplasma genitalium, encodes 480 proteins, of which no fewer than 101 have been ascribed a function in protein synthesis (Fraser et al. 1995; Hutchison et al. 1999). Excluding genes that are less directly involved in translation per se (e.g., those for proteases and peptidases), M. genitalium has about 90 genes encoding proteins in the translation system. Additionally, 37 genes specify RNA molecules, chiefly ribosomal and transfer RNAs (rRNA and tRNAs), which fill critical translational roles. Thus, some 127 genes, a quarter...