The elongation, termination, and recycling phases of translation in eukaryotes

Abstract

This work summarizes our current understanding of the elongation and termination/recycling phases of eukaryotic protein synthesis. We focus here on recent advances in the field. In addition to an overview of translation elongation, we discuss unique aspects of eukaryotic translation elongation including eEF1 recycling, eEF2 modification, and eEF3 and eIF5A function. Likewise, we highlight the function of the eukaryotic release factors eRF1 and eRF3 in translation termination, and the functions of ABCE1/Rli1, the Dom34:Hbs1 complex, and Ligatin (eIF2D) in ribosome recycling. Finally, we present some of the key questions in translation elongation, termination, and recycling that remain to be answered.

Figure 1.

Model of the eukaryotic translation elongation pathway. In this model the large ribosomal subunit is drawn transparent to visualize tRNAs, factors, and mRNA binding to the decoding center at the interface between the large and small subunits and tRNAs interacting with the peptidyl transferase center in the large subunit. Starting at the top, an eEF1A·GTP·aminoacyl-tRNA ternary complex binds the aminoacyl-tRNA to the 80S ribosome with the anticodon loop of the tRNA in contact with the mRNA in the A site of the small subunit. Following release of eEF1A·GDP, the aminoacyl-tRNA is accommodated into the A site, and the eEF1A·GDP is recycled to eEF1A·GTP by the exchange factor eEF1B. Peptide bond formation is accompanied by transition of the A- and P-site tRNAs into hybrid states with the acceptors ends of the tRNAs moving to the P and E sites, respectively. Binding of eEF2·GTP promotes translocation of the tRNAs into the canonical P and E sites, and is followed by release of eEF2·GDP, which unlike eEF1A does not require an exchange factor. The ribosome is now ready for the next cycle of elongation with release of the deacylated tRNA from the E site and 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 positions of the mRNA, tRNAs, and factors are drawn for clarity and are not meant to specify their exact places on the ribosome.

Figure 2.

Model of the eukaryotic translation termination and recycling pathways. In this model the large ribosomal subunit is drawn as transparent to visualize tRNAs, factors, and mRNA binding to the decoding center at the interface between the large and small subunit. Throughout, GTP is depicted as a green ball and GDP as a red ball; also, the positions of the mRNA, tRNAs, and factors are drawn for clarity and are not meant to specify their exact places on the ribosome. On recognition of a stop codon, the eRF1:eRF3:GTP ternary complex binds to the A site of the ribosome in a preaccommodated state, GTP hydrolysis occurs, and eRF3 is released. ABCE1/Rli1 binds and facilitates the accommodation of eRF1 into an optimally active configuration.