{"doi":"10.1101/2022.11.16.515324","title":"A conserved sequence in <i>Drosophila</i> Argonaute1 mRNA contributes to stress response via inducing miR-999 degradation","abstract":"Abstract MicroRNAs (miRNAs) load onto Argonaute (AGO) proteins and target messenger RNAs (mRNA) to directly suppress gene expression at the post-transcriptional level. However, miRNA degradation can be triggered when there is extended base-pairing between miRNAs and the target RNAs. Such base-pairing can induce confirmational change of AGO and recruitment of ZSWIM8 ubiquitin ligase to mark AGO for proteasomal degradation, while the miRNAs are subsequently degraded. This target RNA-directed miRNA degradation (TDMD) mechanism appears to be an evolutionary conserved mechanism, but recent studies have focused on identifying endogenous TDMD events in the mammalian systems. Here, we performed AGO1-CLASH (crosslinking and sequencing of miRNA-mRNA hybrids) in Drosophila S2 cells, with Dora (ortholog of vertebrate ZSWIM8) knockout (KO) mediated by CRISPR-Cas9 to identify five TDMD triggers (sequences that can induce miRNA degradation). Interestingly, one trigger residing in the 3′ UTR of AGO1 mRNA induces miR-999 degradation. CRISPR-Cas9 KO of the AGO1 trigger in S2 cells and in Drosophila elevates miR-999 abundance, with concurrent repression of the miR-999 targets. AGO1 trigger-KO flies respond poorly to hydrogen peroxide-induced stress, demonstrating the physiological importance of a single TDMD event.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":313164,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"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":691205,"name":"Lu Li","orcid":"0000-0001-9925-0138","position":1,"is_corresponding":false},{"id":720319,"name":"Tianqi Li","orcid":"0000-0003-3919-0211","position":2,"is_corresponding":false},{"id":236488,"name":"Yuzhi Wang","orcid":"0000-0003-3552-1589","position":3,"is_corresponding":false},{"id":720318,"name":"Nicholas M. Hiers","orcid":"0000-0003-0996-364X","position":4,"is_corresponding":false},{"id":1011865,"name":"Jennifer S. Mejia","orcid":null,"position":5,"is_corresponding":false},{"id":1011866,"name":"Jossie S. Sanchez","orcid":null,"position":6,"is_corresponding":false},{"id":666831,"name":"Lei Zhou","orcid":"0000-0001-8251-3974","position":7,"is_corresponding":false},{"id":720323,"name":"Mingyi Xie","orcid":"0000-0001-7955-197X","position":8,"is_corresponding":false},{"id":720320,"name":"Peike Sheng","orcid":"0000-0003-1324-8606","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:33:44.454239Z","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":[]}