Figure 1. Ribosomes are remodeled: examples of RP phosphorylation and ubiquitylation events.

(a) Phosphorylation (represented by −P) of Rps6 has been observed downstream of multiple growth signals and pharmacological stimuli. The functional role of Rps6 phosphorylation has been elucidated in mouse models lacking Rps6 phosphorylation sites. Phosphorylation of Rpl13a occurs as part of the innate immune response and leads to the separation of this RP from assembled ribosomes to carry out a transcript-specific translation program as part of the GAIT complex. Rpl13a phosphorylation has been identified in human monocytic cells. Phosphorylation of Rps15 is critical for the neurotoxicity phenotype seen in Parkinson’s disease models in human neurons and Drosophila. Pencil symbol denotes the enzymes responsible for attaching the PTM to the RPs, whereas scissors symbol denotes the enzymes reversing the PTM. Pencil or scissors symbols in green indicates that the specific enzymes are known for this particular PTM; whereas pencil or scissors in white indicates the enzymes remain unknown.

(b) Ubiquitin modifications (represented by magenta circles) at the ribosome can lead to diverse outcomes: non-degradative K63 linked ubiquitin chains or mono-ubiquitin signals can modify RPs in response to stress conditions. For example, in response to oxidative stress in yeast, RPs are modified by K63 linkages. Upon ER stress, cytoplasmic ribosomes, but not ER-ribosomes are decorated with mono-ubiquitin on multiple different RPs as shown in a tissue-culture based system. Ubiquitin signaling at the ribosome as part of the mRNA-protein quality control pathway is versatile and can modify nascent chains with degradative K48-linked ubiquitin chains while also modifying RPs with mono-ubiquitin signals. Ubiquitin signaling can also mark ribosome biogenesis factors and may lead to ribosome functional diversity during neural crest cell differentiation.