Ribosome Assembly and Repair

Abstract

Ribosomes synthesize protein in all cells. Maintaining both the correct number and composition of ribosomes is critical for protein homeostasis. To address this challenge, cells have evolved intricate quality control mechanisms during assembly to ensure that only correctly matured ribosomes are released into the translating pool. However, these assembly-associated quality control mechanisms do not deal with damage that arises during the ribosomes' exceptionally long lifetimes and might equally compromise their function or lead to reduced ribosome numbers. Recent research has revealed that ribosomes with damaged ribosomal proteins can be repaired by the release of the damaged protein, thereby ensuring ribosome integrity at a fraction of the energetic cost of producing new ribosomes, appropriate for stress conditions. In this article, we cover the types of ribosome damage known so far, and then we review the known repair mechanisms before surveying the literature for possible additional instances of repair.

Keywords: ribosomal protein chaperone; ribosomal protein turnover; ribosome assembly; ribosome damage; ribosome repair; ribosome turnover.

Figure 1.. The location of ribosomal proteins with chaperones or evidence of damage.

(A) RPs with known personalized chaperones are highlighted in multiple colors and in space-fill in yeast 80S ribosomes (from PDB ID 4V88). The small ribosomal subunit is shown in cyan and the large subunit in pink. (B) RPs frequently oxidized are shown in multiple colors and are highlighted in multiple colors and space-fill as in panel A.

Figure 2.. Model for ribosome repair.

Oxidative stress preferentially damages eS26/Rps26 and uL16/Rpl10 in yeast. Ribosomes containing the damaged proteins are removed from the polysomes and converted into idle 80S complexes, from which Tsr2 and Sqt1 release eS26/Rps26 and uL16/Rpl10, respectively. Newly-made eS26/Rps26 and uL16/Rpl10 are then incorporated into these ribosomes to repair the lesion and allow for resumption of translation by these subunits. Adapted from (Yang et al 2023).

Figure 3:. Chaperone-dependent ribosome remodeling.

(A) Tsr2-dependent release of eS26/Rps26 under high salt or pH stress produces eS26-deficient ribosomes (Yang & Karbstein 2022), which have altered mRNA selectivity (Ferretti et al 2017), and support the translation of mRNAs encoding for proteins involved in the response to high salt/pH stress. (B) Oxidation of the Zn-finger cysteines in eS26/Rps26 leads Zn-release, partial protein unfolding, thus weakening its binding to ribosomes, and enabling its release by Tsr2 (Yang et al 2023). (C) Highlight of the structure of eS26/Rps26 within ribosomes (from PDB ID 4V88). The Zn²⁺, and Mg²⁺ ions that support the folding and binding of eS26/Rps26, respectively, are highlighted. (D) Model for Na⁺-dependent release of eS26/Rps26. Mg²⁺ binding to Asp33 is required for eS26 binding (Schutz et al 2014). Na⁺ competes for this Mg²⁺ ion (Yang & Karbstein 2022), weakening eS26/Rps26 binding to ribosomes, while strengthening binding to Tsr2 (Schutz et al 2018), enabling Tsr2-mediated release of eS26/Rps26 at high salt.