The E3 ubiquitin ligase RNF10 modifies 40S ribosomal subunits of ribosomes compromised in translation
Description
Reversible monoubiquitination of small subunit ribosomal proteins RPS2 and RPS3 has been noted to occur on ribosomes involved in ZNF598-dependent mRNA surveillance. 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. These impeded ribosomes are tagged by ubiquitin at their 40S subunit for subsequent programmed degradation unless rescued by USP10.