This chapter has described the translation of information encoded in the nucleotide sequence of an mRNA into the amino acid sequence of a protein. Our proteins, more than any other macromolecule, determine who we are and what we are. They are the enzymes responsible for cell metabolism, including DNA and RNA synthesis, and are the regulatory factors required for the expression of the genetic program. The versatility of proteins as biological molecules is manifested in the diversity of shapes that they can assume. Furthermore, even after they are synthesized, they can be modified in a variety of ways by the addition of molecules that can alter their function.

Given the central role of proteins in life, it is not surprising that both the genetic code and the machinery for translating this code into protein have been highly conserved from bacteria to humans. The major components of translation are three classes of RNA: tRNA, mRNA, and rRNA. The accuracy of translation depends on the enzymatic linkage of an amino acid with its cognate tRNA, generating a charged tRNA molecule. As adapters, tRNAs are the key molecules in translation. In contrast, the ribosome is the factory where mRNA, charged tRNAs, and other protein factors come together for protein synthesis.

The key decision in translation is where to initiate translation. In prokaryotes, the initiation complex assembles on mRNA at the Shine–Dalgarno sequence, just upstream of the AUG start codon. The initiation complex in eukaryotes is assembled at the 5′ cap structure of the mRNA and moves in a 3′ direction until the start codon is recognized. The longest phase of translation is the elongation cycle; in this phase, the ribosome moves along the mRNA, revealing the next codon that will interact with its cognate-charged tRNA so that the charged tRNA’s amino acid can be added to the growing polypeptide chain. This cycle continues until a stop codon is encountered. Release factors facilitate translation termination.

In the past few years, new imaging techniques have revealed ribosomal interactions at the atomic level. With these new “eyes,” we can now see that the ribosome is an incredibly dynamic machine that changes shape in response to the contacts made with tRNAs and with proteins. Furthermore, imaging at atomic resolution has revealed that the ribosomal RNAs, not the ribosomal proteins, are intimately associated with the functional centers of the ribosome.

The proteome is the complete set of proteins that can be expressed by the genetic material of an organism. Whereas a typical multicellular eukaryote has about 20,000 genes, the typical proteome is probably 10- to 50-fold larger. This difference is in part the result of posttranslational modifications such as phosphorylation and ubiquitination, which influence protein activity and stability.