Figure 2.

The eukaryotic translation cycle. Ribosomal biogenesis (lavender) starts in the nucleolus and ends in the cytoplasm, where mature translation-competent cytoplasmic eukaryotic 40S and 60S ribosomal subunits are being released. Ribosomal protein translation proceeds in cycles of four stages: translation initiation (red), elongation (yellow), and termination (blue) followed by ribosomal recycling (green). During initiation, the SSU attaches to an mRNA, either via the canonical (eIF1–5) eukaryotic translation initiation factor-dependent pathway or via alternative eIF2D/malignant T-cell amplified protein 1 (MCT-1)/density-regulated protein (DENR) or internal ribosomal entry site (IRES)-mediated (re-) initiation, whereas the 60S ribosomal subunit is prevented from premature reassociation with the 40S by eIF6 until the correct start codon has been recognized by the initiator tRNA. Then, the two subunits associate and the 80S ribosome translates the open reading frame (ORF) of the mRNA in repetitive cycles of elongation/translocation until it either stalls prematurely in case of a truncated mRNA, which triggers the Hbs1–Pelota-dependent rescue pathway, or at a normal stop codon, leading to translation termination. In both cases, the ribosomal subunits are being split by the ATPase ABCE1 and detached from mRNA and remaining deacylated tRNAs, such that they can engage in another round of translation initiation on either the same or a different mRNA. Some translation factors act as GTPases, which catalyze GTP-dependent reactions and therefore mark energy-consuming irreversible checkpoints along the trajectory of the translational cycle (pink stars). IC, initiation complex.