Translation Elongation and Recoding in Eukaryotes

Abstract

In this review, we highlight the current understanding of translation elongation and recoding in eukaryotes. In addition to providing an overview of the process, recent advances in our understanding of the role of the factor eIF5A in both translation elongation and termination are discussed. We also highlight mechanisms of translation recoding with a focus on ribosomal frameshifting during elongation. We see that the balance between the basic steps in elongation and the less common recoding events is determined by the kinetics of the different processes as well as by specific sequence determinants.

Figure 1.

Model of the eukaryotic translation elongation pathway. At the top, an eEF1A•GTP•aminoacyl-tRNA (transfer RNA) ternary complex binds to the A (aminoacyl) site of an 80S ribosome with the anticodon loop of the tRNA in contact with the messenger RNA (mRNA). Following GTP hydrolysis and release of an eEF1A•GDP binary complex, the aminoacyl-tRNA is accommodated into the A site, and the eEF1A•GDP is recycled to eEF1A•GTP by the exchange factor eEF1B. During catalysis of peptide bond formation, the A- and P (peptidyl)-site tRNAs shift into hybrid states with the acceptor ends of the tRNAs moving to the P and E sites, respectively. Substrate positioning for peptide bond formation is aided by binding of the factor eIF5A and its hypusine modification (green) in the E site. Following peptide bond formation, the factor eEF2•GTP with its diphthamide modification (magenta) binds in the A site and promotes translocation of the tRNAs into the canonical P and E sites. Following release of the deacylated tRNA from the E site, the next cycle of elongation commences with binding of the appropriate eEF1A•GTP•aminoacyl-tRNA to the A site. Throughout, GTP is depicted as a green ball and GDP as a red ball; also, the large ribosomal subunit (light blue) is displayed transparently to enable visualization of the tRNAs, factors, and mRNA bound to the decoding center at the interface between the large and small subunits and of tRNAs, interacting with the peptidyl transferase center in the large subunit. Note, however, that the positions of the mRNA, tRNAs, and factors are drawn for clarity and are not meant to specify their exact places on the ribosome.