Figure 4.
Ribosome ubiquitination as a trigger of quality control systems induced by ribosome stalling. Left: In RQC, the critical E3 ubiquitin ligase Hel2 and its mammalian homolog ZNF598 recognize disomes containing colliding ribosomes in the rotated state (73,79), leading to ubiquitination of uS10 in yeast and uS10, eS10, and uS3 in mammals. Right: In 18S NRD, non-functional 80S ribosomes containing the A1492C mutation in the decoding center stall due to decoding failures and are sequentially ubiquitinated at the K212 residue of uS3. Mag2 monoubiquitinates uS3 at K212, followed by Hel2-mediated polyubiquitination. Subsequently, the Ski2-like RNA helicase Slh1 in the RQT complex stimulates subunit dissociation to promote Xrn1-dependent degradation of the non-functional 18S rRNA in the 40S subunit (100). In these quality control systems, the ribosome is stalled at the specific conformation, and the specific E3 ligases recognize and ubiquitinate particular sites to induce the subsequent quality control steps.