{"doi":"10.1101/2021.01.19.427285","title":"Translation Inhibitory Elements from Hox a3 and a11 mRNAs use uORFs for translation inhibition","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>During embryogenesis, Hox mRNA translation is tightly regulated by a sophisticated molecular mechanism that combines two RNA regulons located in their 5’UTR. First, an Internal Ribosome Entry Site (IRES) enables cap-independent translation. The second regulon is a Translation Inhibitory Element or TIE, which ensures concomitant cap-dependent translation inhibition. In this study, we deciphered the molecular mechanisms of Hox a3 and a11 TIE elements. Both TIEs possess an upstream Open Reading Frame (uORF) that is critical to inhibit cap-dependent translation. However, the molecular mechanisms used are different. In TIE a3, we identify a uORF which inhibits cap-dependent translation and we show the requirement of the non-canonical initiation factor eIF2D for this process. The mode of action of TIE a11 is different, it also contains a uORF but it is a minimal uORF formed by an uAUG followed immediately by a stop codon, namely a ‘start-stop’. The a11 ‘start-stop’ sequence is located upstream of a highly stable stem loop structure which stalls the 80S ribosome and thereby inhibits cap-dependent translation of Hox a11 main ORF.</jats:p>","journal":null,"year":null,"id":22281,"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":1,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":138903,"name":"Laure Schaeffer","orcid":null,"position":1,"is_corresponding":false},{"id":138905,"name":"Gilbert Eriani","orcid":null,"position":2,"is_corresponding":false},{"id":60324,"name":"Franck Martin","orcid":"0009-0002-8598-8443","position":3,"is_corresponding":false},{"id":140595,"name":"Fatima Alghoul","orcid":"0000-0003-1934-9483","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":1,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34076576","pmcid":null,"openalex_id":"https://openalex.org/W3122284665","authors":[],"funders":[{"funder_name":"French National Research Agency (ANR)","grant_id":"ANR-17-CE12-0025","title":"Using microfluidics to decipher molecular mechanisms regulating translation machineries"}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/01/21/2021.01.19.427285.full.pdf","host_type":"repository"},{"url":"https://doi.org/10.7554/elife.66369","host_type":"GREEN"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/01/21/2021.01.19.427285.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2021.01.19.427285","host_type":"publisher"},{"url":"https://doi.org/10.1101/2021.01.19.427285","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34076576","host_type":""},{"url":"http://dx.doi.org/10.7554/eLife.66369","host_type":""},{"url":"https://doaj.org/article/1e091babbcc84a9788bac47db31d2610","host_type":""},{"url":"https://dx.doi.org/10.1101/2021.01.19.427285","host_type":""},{"url":"https://dx.doi.org/10.7554/elife.66369","host_type":""}],"fields_of_study":["RNA and protein synthesis mechanisms","RNA Research and Splicing","RNA modifications and cancer","Biology","Medicine","0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":[],"keywords":["Five prime untranslated region","Translation (biology)","Internal ribosome entry site","Eukaryotic translation","Start codon","Upstream open reading frame","Biology","Regulon","Open reading frame","Hox gene","Protein biosynthesis","Genetics","Untranslated region","Cell biology","Messenger RNA","Regulation of gene expression","Gene","Gene expression","Peptide sequence","RNA Caps","QH301-705.5","Science","Eukaryotic Initiation Factor-2","translation","hox mRNA","Internal Ribosome Entry Sites","Open Reading Frames","Structure-Activity Relationship","Biochemistry and Chemical Biology","Animals","Humans","human","RNA, Messenger","Biology (General)","Homeodomain Proteins","TIE","Q","R","Gene Expression Regulation, Developmental","HEK293 Cells","ribosome","Codon, Terminator","Medicine","Nucleic Acid Conformation","Rabbits","5' Untranslated Regions","Ribosomes","uORF"],"sdg_mappings":[{"sdg_number":8,"sdg_label":"8. Economic growth"}],"linked_datasets":[{"doi":"10.5061/dryad.j3tx95xdg","title":"Translation Inhibitory Elements from Hoxa3 and Hoxa11 mRNAs use uORFs for translation inhibition","publisher":"Dryad","resource_type":"Dataset"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-06T18:32:42.158579Z","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":[]}