The eukaryotic ribosome: current status and challenges

Abstract

Despite having been identified first, their greater degree of complexity has resulted in our understanding of eukaryotic ribosomes lagging behind that of their bacterial and archaeal counterparts. A much more complicated biogenesis program results in ribosomes that are structurally, biochemically, and functionally more complex. However, recent advances in molecular genetics and structural biology are helping to reveal the intricacies of the eukaryotic ribosome and to address many longstanding questions regarding its many roles in the regulation of gene expression.

FIGURE 1.

Comparison of yeast and T. thermophilus ribosomes. Yeast ribosome structures (Protein Data Bank codes 1s1h and 1s1i) were obtained by docking atomic models for RNA and protein components into a 11.7-Å cryo-EM map and subsequent threading onto atomic resolution structure of archaeal ribosomes. T. thermophilus ribosome structures (Protein Data Bank codes 2b64 and 2b66) were obtained by x-ray diffraction at a resolution of 5.90 Å. Note the overall larger size and greater density of the yeast ribosomes. SSU, small subunit; LSU, large subunit.

FIGURE 2.

Model of post-translational acetylation and deacetylation of eukaryotic ribosomes. Step 1, pre-rRNA is transcribed in the nucleolus, whereas rRNAs encoding RPs are transcribed in the nucleus. Step 2, cotranslational N-terminal acetylation (NAT) of RPs occurs in the cytoplasm. endo-Acetylases (EndoAc) may also be active. Step 3, mature RPs are re-imported into the nucleolus via the nucleus. We propose that they are deacetylated along this pathway (exactly where is unknown, as shown by presence of deacetylases in both compartments). Deacetylation (DAC) eliminates negative charges on RPs, which could promote charge repulsion with phosphate groups of pre-rRNAs and structure in regions of RPs that need to be unstructured for assembly with rRNA. Step 4, deacetylated, highly basic RPs can properly associate with pre-rRNAs to begin nucleation of pre-ribosomes, rRNA processing, and ribosome biogenesis. Step 5, regulation. Excess free RPs are deacetylated in the nucleus or nucleolus, where they are targeted to the proteasome for degradation. Step 6, dysregulation. Loss of deacetylase activity, e.g. in mof6-1 or rpd3Δ cells (40), interferes with Step 5, resulting in delayed rRNA processing and ribosome (Ribo.) biogenesis defects.