Work

UFMylation orchestrates spatiotemporal coordination of RQC at the ER

Year: 2025

Type: article

Abstract: Degradation of arrest peptides from endoplasmic reticulum (ER) translocon-bound 60 S ribosomal subunits via the ribosome-associated quality control (ER-RQC) pathway requires covalent modification of RPL26/uL24 on 60 S ribosomal subunits with UFM1. However, the underlying mechanism that coordinates the UFMylation and RQC pathways remains elusive. Structural analysis of ER-RQC intermediates revealed concomitant binding and direct interaction of the UFMylation and RQC machineries on the 60 S . In the presence of an arrested peptidyl–transfer RNA, the RQC factor NEMF and the UFM1 E3 ligase (E3 UFM1 ) form a direct interaction via the UFL1 subunit of E3 UFM1 , and UFL1 adopts a conformation distinct from that previously observed for posttermination 60 S . While this concomitant binding occurs on translocon-bound 60 S , LTN1 recruitment and arrest peptide degradation require UFMylation-dependent 60 S dissociation from the translocon. These data reveal a mechanism by which the UFMylation cycle orchestrates ER-RQC.

Source: Science Advances

DOI: 10.1126/sciadv.adv0435