The ribosome ubiquitination code: fine-tuning translation under stress

It has become evident that a complex code of ribosome ubiquitination regulates protein synthesis, particularly in stress conditions. Ubiquitin is known largely for its role in protein stability; however, new high-throughput screening and advances in proteomics are underscoring its novel role as a master regulator of ribosome function. Still, much remains to be discovered about how this code acts and supports translation reprogramming in a context-specific manner. Here we discuss the nature of this code, the dynamics of site-specific ribosome ubiquitination, and the unique roles that multiple enzymes play in defining the translatome and cotranslational quality control pathways. We also provide insights on the importance of unraveling this code to understand the physiological impact of modified ribosome subpopulations in cellular stress and human disease.