The RNA-Binding Function of Ribosomal Proteins and Ribosome Biogenesis Factors in Human Health and Disease

Abstract

The ribosome is a macromolecular complex composed of RNA and proteins that interact through an integrated and interconnected network to preserve its ancient core activities. In this review, we emphasize the pivotal role played by RNA-binding proteins as a driving force in the evolution of the current form of the ribosome, underscoring their importance in ensuring accurate protein synthesis. This category of proteins includes both ribosomal proteins and ribosome biogenesis factors. Impairment of their RNA-binding activity can also lead to ribosomopathies, which is a group of disorders characterized by defects in ribosome biogenesis that are detrimental to protein synthesis and cellular homeostasis. A comprehensive understanding of these intricate processes is essential for elucidating the mechanisms underlying the resulting diseases and advancing potential therapeutic interventions.

Keywords: DBA; RNA-binding proteins; SBDS; ribosomal RNA; ribosomal origins and evolution; ribosomopathies.

Figure 1

Schematic depiction of the evolutionary distribution of ribosomal proteins across superkingdoms. Universal ribosomal proteins are depicted in white within the central area of the three intersecting circles. Ribosomal proteins specific to bacteria are located within the purple section of the lower circle, while those specific to eukaryotes can be found in the light blue section on the left. Ribosomal proteins exclusive to archaea are situated within the region emerging from the overlapping light blue and green circles. Notably, all archaea-specific ribosomal proteins are also present in eukarya, indicating the absence of any ribosomal proteins unique to archaea. The nomenclature of ribosomal proteins is consistent with the literature criteria [11].

Figure 2

Functional ribosome cores are universally conserved in all living systems. (a) A three-dimensional representation of the pseudo-symmetry within the peptidyl transferase center (PTC) is depicted in 2D structure and ribbons. The structural representations were extracted from the cryo-EM data obtained for ribosomes from E. coli (PDB ID: 7K00) and H. sapiens (PDB ID: 4UG0), as depicted on the left and right sides of the figure, respectively. The visualization was generated using UCSF Chimera [21]. Two-dimensional structures of PTC were generated using R2DT software (Version 1.4) [22]. Bases corresponding to the P-site and A-site are denoted by green and light blue letters, respectively, while bases delineating the PTC pore are highlighted in red. This color scheme is consistently maintained throughout the figure. P and A represent two of three active sites of ribosome corresponding to peptidyl and aminoacyl site, respectively. (b) In evidence, PTC mapped into the large ribosomal subunit and superimposed.

Figure 3

The structure of ribosomes. A side-by-side comparison of the structures of prokaryotic (E. coli, pdb ID 7K00) and eukaryotic (H. sapiens, pdb ID: 6QZP) ribosomes. Ribosomes consist of the large (blue) and the small (red) subunit which comprise a combination of ribosomal RNA (rRNA) molecules and proteins. The rRNA molecules provide the basic building block of the ribosome, establishing its basic structure and functional characteristics. The ribosomal proteins contribute to the overall stability and integrity of the ribosome by bridging structural gaps and promoting the efficient synthesis of proteins [53,54,55]. At the center of the figure, rRNA backbone ribbons extracted from superimposed large ribosomal subunits display noticeable variations in size compared to their conserved three-dimensional conformation. The bacterium (E. coli) is green, and the eukaryote (H. sapiens) is blue.