Principles of translational control: an overview

Abstract

Translational control plays an essential role in the regulation of gene expression. It is especially important in defining the proteome, maintaining homeostasis, and controlling cell proliferation, growth, and development. Numerous disease states result from aberrant regulation of protein synthesis, so understanding the molecular basis and mechanisms of translational control is critical. Here we outline the pathway of protein synthesis, with special emphasis on the initiation phase, and identify areas needing further clarification. Features of translational control are described together with numerous specific examples, and we discuss prospects for future conceptual advances.

Figure 1.

Pathway of protein synthesis in bacteria. The simplified cartoon shows the four phases of protein synthesis and how the ribosomes, tRNAs, mRNA, and GTP interact. Not shown are the initiation, elongation, and termination factors that promote the reactions. Following initiation, each turn of the elongation cycle results in the addition of another amino acid (gray pentagon) to the growing peptide chain (not shown). Termination occurs when a termination codon (UAA, UAG, UGA) appears in the ribosomal A-site and involves hydrolysis of the peptidy-tRNA in the P-site. (Figure constructed by Nancy Villa, University of California, Davis.)

Figure 2.

Pathway of eukaryotic initiation. The simplified cartoon shows two types of initiation mechanisms (m⁷G-cap-dependent scanning and IRES-dependent internal), and how the ribosomes, methionyl-tRNA_i, mRNA, and ATP/GTP interact. Not shown are the initiation factors or the possibility that scanning follows IRES-directed binding of the 40S ribosomal subunit during internal initiation. (Figure constructed by Nancy Villa, University of California, Davis.)