LISTERIN E3 Ubiquitin Ligase and Ribosome-Associated Quality Control (RQC) Mechanism

RPL26/uL24 UFMylation is essential for ribosome-associated quality control at the endoplasmic reticulum

“…Ribosomes that stall during protein synthesis are incapacitated by toxic tRNA-bound APs which must be destroyed in order to avert proteotoxicity and to enable reuse of 60S subunits (7,9,72). When stalls occur during translation of cytosolic proteins, these APs are efficiently recognized and ubiquitylated by the well-defined RQC pathway and destroyed by the 26S proteasome, releasing a "rescued" 60S ribosomal subunit competent to undergo further rounds of protein synthesis (7)(8)(9)(10)(33)(34)(35)…”

“…Ribosomes that stall during protein synthesis are incapacitated by toxic tRNA-bound APs which must be destroyed in order to avert proteotoxicity and to enable reuse of 60S subunits (7, 9, 72). When stalls occur during translation of cytosolic proteins, these APs are efficiently recognized and ubiquitylated by the well-defined RQC pathway and destroyed by the 26S proteasome, releasing a “rescued” 60S ribosomal subunit competent to undergo further rounds of protein synthesis (7–10, 33–35) (Fig 1A). However, stalls that occur on ribosomes engaged in cotranslational translocation of proteins into the ER generate ER-APs that are shielded from cytosolic UPS machinery by the RTJ (Fig 1B) and disrupt protein translocation in addition to ribosome function (1, 2).…”

“…Alternatively, CAT tails can autonomously function as degrons to enable ubiquitylation by cytosolic E3s, promoting degradation of APs after their release from the 60S subunit (30,32). How the RQC pathway resolves stalled APs on cytosolic ribosomes has been investigated in considerable detail and is the subject of several recent reviews (7)(8)(9)(33)(34)(35). By contrast, the role of RQC in resolving stalled ribosomes engaged in cotranslational translocation of proteins across the membrane of the endoplasmic reticulum (ER) has been relatively unexplored.…”

Argonaute-dependent ribosome-associated protein quality control

“…Of note, the binding between Ltn1 and the 60S ribosomal subunits is specific and is critical for RQC [36]. This binding provides a faithful step during RQC in which Ltn1 specifically recognizes its substrates, allowing only arrested nascent peptides that are still associated with stalled 60S ribosomes to be ubiquitinated [38]. Consistent with its critical role in RQC, genetic studies have revealed the importance of Ltn1 in neuronal tissue homeostasis, since Ltn1 mutant mice displayed various neurological disorders, which are likely attributed to protein aggregation caused by Ltn1 loss of function [39].…”

RPL26/uL24 UFMylation is essential for ribosome-associated quality control at the endoplasmic reticulum

“…Alternatively, CAT tails can autonomously function as degrons to enable ubiquitylation by cytosolic E3s, promoting degradation of APs after their release from the 60S subunit ( 24 , 26 ). How the RQC pathway resolves stalled APs on cytosolic ribosomes has been investigated in considerable detail and is the subject of several recent reviews ( 1 – 3 , 27 – 29 ). By contrast, the role of RQC in resolving stalled ribosomes engaged in cotranslational translocation of proteins across the membrane of the endoplasmic reticulum (ER) has been relatively unexplored.…”