Fig. 8: Model of dwell time dependent selection of disomes/trisomes for the RQC pathway.

a Hel2 binds to translating ribosomes with low affinity. b A translating ribosome encounters a stalling-prone mRNA sequence. c A trailing ribosome catches up and collides with the stalled ribosome forming a disome. Hel2 binds with increased affinity to the disome and initiates ubiquitination of the 40S ribosomal protein Rps20. d The leading ribosome resumes translation, Hel2 reverts to its low-affinity binding mode, and ubiquitination of Rps20 ceases. e The deubiquitinases Ubp2 and Ubp3 remove ubiquitin chains from Rps20. This may occur during translation and/or after translation termination. f In case the leading ribosome stalls for a prolonged period of time, the disome develops the Asc1-Asc1 platform, which results in further increased affinity of Hel2. Hel2 now continuously extends the polyubiquitin chain until the RQC and NGD machineries are recruited and resolve the stalled ribosome. Hel2 in yellow, Asc1 in orange, Rps20 in white, ubiquitin moieties in red. For details see Discussion.