Translation and the Genetic Code

  Once in the cytoplasm, mRNA serves as a template for protein synthesis, or translation, which occurs in macromolecular complexes called ribosomes. In these microscopic assembly lines, the nucleotide sequence in mRNA is read and translated into an amino acid sequence. During this process, the cell converts the four-base mRNA code into 20 amino acids language of proteins. Remarkably, all cells use the same genetic code to specify the order in which amino acids enter the growing protein chain. This code is a triplet of bases, the codon. Permutations of the four nucleotides in RNA result in 64 different triplets (4 x 4 x 4), such that any one of the 20 amino acids may be specified by more than one codon, (e.g., cysteine = UGU or UGC).

  The conversion of a nucleic acid code into an amino acid code requires adapter molecules, called transfer RNA (tRNA), to decode mRNA. Each small tRNA molecule carries a specific amino acid to the protein-synthesizing machinery of the ribosome, and each tRNA uses a unique three-base "anticodon" to line up with the complementary codon in mRNA (Figure 1, bottom). Ribosomal enzymes link adjoining amino acids, thereby freeing them from their tRNA adapters, and add them to the growing amino acid chain in the order designated by the order of codons in the mRNA template. Translation thus completes the transfer of genetic information from the gene to a unique protein structure. The selective translation of transcripts can also be regulated, as can the stability of specific proteins. Post-translational modifications are also important modulators of protein function. Post-transcriptional regulatory processes are generally emerging as key control points in the cardiovascular system as well as in many other tissues, and are likely to be particularly important in response to signals from outside the cell.

  The universality of the mechanisms underlying the flow of genetic information has important medical ramifications. The basic process by which a cell produces proteins from genes vary little in the biological world, which means that human cellular function can often be inferred from the study of other organisms. Moreover, human genes can be introduced into any number of different cell types, enabling human proteins to be mass-produced in bacteria or yeast, or expressed in animal models of disease. The unifying principles underlying DNA structure and function are therefore crucial to the further manipulation of genetic material.