SAYSD1 senses UFMylated ribosome to safeguard co-translational protein translocation at the endoplasmic reticulum

• DOI: 10.1016/j.celrep.2023.112028
• Publication Date: 2023-01-23T17:28:19Z
• Authors: Lihui Wang; Yue Xu; Sijung Yun; Quan Yuan; Prasanna Satpute-...; Yihong Ye
• Keywords: 0301 basic medicine; 0303 health sciences; QH301-705.5; Membrane Proteins; Fenbendazole; Endoplasmic Reticulum; Article; Basement Membrane; Protein Transport; 03 medical and health sciences; Animals; Drosophila Proteins; CP: Molecular biology; Drosophila; Biology (General); Ribosomes

Translocon clogging at the endoplasmic reticulum (ER) as a result of translation stalling triggers ribosome UFMylation, activating translocation-associated quality control (TAQC) to degrade clogged substrates. How cells sense UFMylation initiate TAQC is unclear. We conduct genome-wide CRISPR-Cas9 screen identify an uncharacterized membrane protein named SAYSD1 that facilitates TAQC. associates with Sec61 translocon and also recognizes both UFM1 directly, engaging stalled nascent chain ensure its transport via TRAPP complex lysosomes for degradation. Like deficiency, depletion causes accumulation translocation-stalled proteins ER stress. Importantly, disrupting UFM1- SAYSD1-dependent in Drosophila leads intracellular collagens, defective collagen deposition, abnormal basement membranes, reduced stress tolerance. Thus, acts sensor collaborates site translocon, safeguarding homeostasis during animal development.