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UFMylation orchestrates spatiotemporal coordination of RQC at the ER
Ivan Penchev1, Samantha Gumbin2, Francesco Scavone2
1Department of Biochemistry, Gene Center, Feodor-Lynen-Str. 25, University of Munich, 81377, Munich, Germany.
Science Advances
|May 2, 2025
Summary
The UFMylation cycle orchestrates the endoplasmic reticulum ribosome-associated quality control (ER-RQC) pathway by coordinating UFMylation and RQC machineries. This process involves the dissociation of 60S ribosomal subunits from the translocon for arrest peptide degradation.
Area of Science:
- Molecular Biology
- Cellular Quality Control Mechanisms
Background:
- The degradation of arrest peptides from ER translocon-bound 60S ribosomal subunits relies on the ER-RQC pathway.
- This pathway necessitates the UFMylation of RPL26/uL24 on 60S ribosomal subunits.
Purpose of the Study:
- To elucidate the mechanism coordinating the UFMylation and ER-RQC pathways.
- To understand the structural basis of ER-RQC pathway regulation.
Main Methods:
- Structural analysis of ER-RQC intermediates.
- Investigating protein-protein interactions between UFMylation and RQC machineries.
Main Results:
- Concomitant binding and direct interaction of UFMylation and RQC machineries on 60S ribosomal subunits were observed.
- NEMF and the UFM1 E3 ligase (E3UFM1) directly interact via UFL1 in the presence of arrested peptidyl-tRNA.
- UFL1 adopts a distinct conformation on translocon-bound 60S compared to posttermination 60S.
Conclusions:
- The UFMylation cycle orchestrates the ER-RQC pathway.
- UFMylation-dependent dissociation of 60S from the translocon is crucial for LTN1 recruitment and arrest peptide degradation.
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