UFMylation orchestrates spatiotemporal coordination of RQC at the ER
Ivan Penchev, Samantha C. Gumbin, Francesco Scavone, Otto Berninghausen, Thomas Becker, Ron R. Kopito, Roland Beckmann
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.