Fig. 5: Model for the eS7 ubiquitination-deubiquitination cycle during translation.
From: Molecular basis for recognition and deubiquitination of 40S ribosomes by Otu2
Shown is a simplified scheme of steps occurring between ribosome recycling and initiation: During active translation, eS7 is monoubiquitinated at Lys83. After termination, the 80S ribosome is dissociated into subunits and a 40S post-splitting complex is formed consisting of ribosome recycling factor ABCE1 in a hybrid conformation and eIF3j. The 43S pre-initiation complex forms by assembly of eIF1, eIF1A, eIF3, and eIF5, followed by binding of the ternary eIF2αβγ-tRNAi-GTP complex. mRNA loading leads to formation of the 48S initiation complex that scans the mRNA until the first AUG codon is recognized. This leads to positioning of the eIF5 N-terminal domain (eIF5-NTD) and dissociation of eIF1. Start codon recognition leads to dissociation of most initiation factors followed by subunit joining. Otu2 engages the SSU as soon as the 80S ribosome is split into subunits and may remain bound to the 40S throughout all stages of initiation until subunit joining. Otu2 hereby plays a role in translational reset of recycled 40S subunits by deubiquitinating Lys83-monoubquitinated eS7. After subunit joining 80S ribosomes are marked as actively elongating ribosomes via eS7-ubiquitination by Not4 of the Ccr4-NOT complex. This marker can be further used as hub for eS7 polyubiquitination by Hel2 in case of aberrant translation and ribosome collision to cause No-Go mRNA decay. “D” and “T” in ABCE1 indicate presence of ATP and ADP in the hybrid state, that ABCE1 adopts in initiation complexes50. “T” in eIF2γ indicates bound GTP. Ub ubiquitin, PABP poly-A binding protein, NP nascent peptide, RFs release factors.
