The E3 ubiquitin ligase RNF10 modifies 40S ribosomal subunits of ribosomes compromised in translation

Subsequent deubiquitination of RPS2 and RPS3 by USP10 is critical for recycling of stalled ribosomes in a process known as ribosome-associated quality control (RQC). Here, we identified and characterized the RPS2- and RPS3-specific E3 ligase RING finger protein 10 (RNF10) and its role in translation.

Overexpression of RNF10 increased 40S ribosomal subunit degradation similar in extent to the knockout of USP10. Although a substantial fraction of RNF10-mediated RPS2 and RPS3 monoubiquitination resulted from ZNF598-dependent sensing of collided ribosomes, ZNF598-independent impairment of translation initiation and elongation also contributed to RPS2 and RPS3 monoubiquitination. PAR-CLIP-based identification of crosslinked mRNA and tRNAs suggests recruitment of RNF10 to fully assembled, though functionally impaired or stalled ribosomes.