{"doi":"10.1101/2022.12.05.519155","title":"SAYSD1 senses UFMylated ribosome to safeguard co-translational protein translocation at the endoplasmic reticulum","abstract":"Abstract Translocon clogging at the endoplasmic reticulum (ER) as a result of translation stalling triggers ribosome UFMylation, activating a T ranslocation- A ssociated Q uality C ontrol (TAQC) mechanism that degrades clogged substrates. How cells sense ribosome UFMylation to initiate TAQC is unclear. Here we use a genome-wide CRISPR/Cas9 screen to identify an uncharacterized membrane protein named SAYSD1 that facilitates TAQC. SAYSD1 associates with the Sec61 translocon, and also recognizes both ribosome and UFM1 directly, engaging a stalled nascent chain to ensure its transport via the TRAPP complex to lysosomes for degradation. Like UFM1 deficiency, SAYSD1 depletion causes the accumulation of translocation-stalled proteins at the ER and triggers ER stress. Importantly, disrupting UFM1- and SAYSD1-dependent TAQC in Drosophila leads to intracellular accumulation of translocation-stalled collagens, defective collagen deposition, abnormal basement membranes, and reduced stress tolerance. Together, our data support a model that SAYSD1 acts as a UFM1 sensor that collaborates with ribosome UFMylation at the site of clogged translocon, safeguarding ER homeostasis during animal development.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":298458,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":239791,"name":"Yue Xu","orcid":"0000-0002-0958-8846","position":1,"is_corresponding":false},{"id":375750,"name":"Sijung Yun","orcid":"0000-0003-1948-3690","position":2,"is_corresponding":false},{"id":660334,"name":"Quan Yuan","orcid":"0000-0002-0676-2079","position":3,"is_corresponding":false},{"id":987513,"name":"Prasanna Satpute‐Krishnan","orcid":"0000-0002-1210-4021","position":4,"is_corresponding":false},{"id":239793,"name":"Yihong Ye","orcid":"0000-0002-9512-7922","position":5,"is_corresponding":false},{"id":786058,"name":"Lihui Wang","orcid":"0000-0002-8479-7859","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:36.269611Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}