SERBP1 is a master regulator of ribosome interactions

Ribosome function depends on interactions with diverse proteins whose activities determine translational efficiency, impose quality control and activate signaling pathways. These many competing activities must in turn be regulated. SERBP1 is an abundant cellular factor that interacts with ribosomes at multiple functionally critical sites on both dormant and active ribosomes. Here, we perform mass spectrometry across sucrose gradients in untreated and stressed cells and find that SERBP1 modulates ribosome interactions with many factors involved in processes including mRNA degradation, translational control, ribosome quality control and ribosome degradation. We then define the role of SERBP1 in protection of ribosomes against selective 40S degradation in the context of mTOR inhibition through its competition with the E3 ligase RNF10 and the atypical kinase RIOK3. Our work reveals SERBP1 as a key player in maintaining ribosome subunit balance and more broadly in the regulation of diverse ribosome activities.