The 80S ribosome stalls during translation (left panel) and, for polybasic substrates (++++ symbol), this is recognized by Asc1 and Hel2 leading to translation termination and possibly RNA cleavage. Ltn1, Rqc1, and Tae2 are then recruited and the 40S subunit disassociates (the order of these events remains to be determined). Ltn1 then ubiquitylates the nascent chain (second panel) leading to recruitment of Cdc48 and its cofactors Npl4 and Ufd1 (third panel). In addition, to its role in substrate ubiquitylation, Tae2 signals translation stress to Hsf1. Levels of Rqc1 are downregulated by the activity of the RQC leading to a negative feedback loop controlling overall activity of the pathway.