Models of eEF3 functions at collided ribosomes. (A) Mbf1 and other quality control regulators oppose eEF3-mediated frameshifting at collided ribosomes. We propose that eEF3 can act on collided ribosomes prior to Mbf1 binding, but that Mbf1 interaction prevents the action of eEF3. Gcn1/Gcn20/Gir2/Rbg2 binding to the Mbf1-bound collided ribosome (Pochopien et al. 2021) likely assists Mbf1 or blocks the interaction of eEF3 due to homologous ribosome binding sites (Marton et al. 1993; Visweswaraiah et al. 2012). Hel2-mediated ubiquitination results in disassembly of the stalled ribosome resulting in depletion of the pool of collided ribosomes. Gcn1 and Hel2 also prevent disassociation of Mbf1 from the collided ribosome, an event which might allow eEF3 to access this ribosome and promote frameshifting. (B) Three models for the mechanisms by which eEF3 may induce frameshifting on collided ribosome. Model 1: eEF3 could effect dissociation of the E site tRNA from the stalled ribosome. Model 2: eEF3 could bind the hybrid collided ribosome to finish the translocation reaction into a POST state, which would increase the force on the mRNA. Model 3: eEF3 could be responsible for driving the collided ribosomes into close contact, closing the gap that traps the colliding ribosome in the hybrid state.
