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. Author manuscript; available in PMC: 2021 Dec 10.
Published in final edited form as: Science. 2020 Apr 17;368(6488):eaay6912. doi: 10.1126/science.aay6912

Fig. 6. Model of cotranslational mRNA degradation.

Fig. 6.

Upon subunit association, eS7 is ubiquitinated by Not4. Ccr4-Not can then be anchored to the ubiquitinated (–/PP/–) ribosome through the Not5-NTD. In the case of successful decoding, the ribosome adopts the rolled (AA/PP/–) conformation, disfavoring Ccr4-Not association. Efficient peptidyl transfer leads to translocation, resulting in a classical posttranslocation state (–/PP/EE). If peptidyl transfer is slow, eIF5A binds to the E-site, promoting PTC activity and rescuing translation. When decoding efficiency is low because of a nonoptimal codon in the A-site, there is an increased probability that the E-site tRNA dissociates before the correct tRNA is accommodated in the A-site, resulting in a (–/PP/–) posttranslocation-state ribosome. This complex is recognized by the Not5-NTD, leading to deadenylation and Dhh1-dependent mRNA degradation. It is unclear whether the mRNA also enters the degradation pathway in the case of the Ccr4-Not–bound initiator ribosome.