{"doi":"10.1101/2023.11.17.567602","title":"<i>JUN</i>\n                  mRNA Translation Regulation is Mediated by Multiple 5’ UTR and Start Codon Features","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>\n                  Regulation of mRNA translation by eukaryotic initiation factors (eIFs) is crucial for cell survival. In humans, eIF3 stimulates translation of the\n                  <jats:italic>JUN</jats:italic>\n                  mRNA which encodes the transcription factor JUN, an oncogenic transcription factor involved in cell cycle progression, apoptosis, and cell proliferation. Previous studies revealed that eIF3 activates translation of the\n                  <jats:italic>JUN</jats:italic>\n                  mRNA by interacting with a stem loop in the 5′ untranslated region (5′ UTR) and with the 5′ -7-methylguanosine cap structure. In addition to its interaction site with eIF3, the\n                  <jats:italic>JUN</jats:italic>\n                  5′ UTR is nearly one kilobase in length, and has a high degree of secondary structure, high GC content, and an upstream start codon (uAUG). This motivated us to explore the complexity of\n                  <jats:italic>JUN</jats:italic>\n                  mRNA translation regulation in human cells. Here we find that JUN translation is regulated in a sequence and structure-dependent manner in regions adjacent to the eIF3-interacting site in the\n                  <jats:italic>JUN</jats:italic>\n                  5′ UTR. Furthermore, we identify contributions of an additional initiation factor, eIF4A, in\n                  <jats:italic>JUN</jats:italic>\n                  regulation. We show that enhancing the interaction of eIF4A with\n                  <jats:italic>JUN</jats:italic>\n                  by using the compound Rocaglamide A (RocA) represses\n                  <jats:italic>JUN</jats:italic>\n                  translation. We also find that both the upstream AUG (uAUG) and the main AUG (mAUG) contribute to\n                  <jats:italic>JUN</jats:italic>\n                  translation and that they are conserved throughout vertebrates. Our results reveal additional layers of regulation for\n                  <jats:italic>JUN</jats:italic>\n                  translation and show the potential of\n                  <jats:italic>JUN</jats:italic>\n                  as a model transcript for understanding multiple interacting modes of translation regulation.\n                </jats:p>","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":null,"id":21701,"datarank":0.11645564715648235,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.012483570072490546,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.012483570072490546,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":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":138799,"name":"Eimy A. Castellanos-Silva","orcid":null,"position":1,"is_corresponding":false},{"id":138800,"name":"Gabriela Díaz-Figueroa","orcid":null,"position":2,"is_corresponding":false},{"id":17801,"name":"Jamie H. D. Cate","orcid":"0000-0001-5965-7902","position":3,"is_corresponding":false},{"id":138798,"name":"Angélica M. González-Sánchez","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38014201","pmcid":null,"openalex_id":"https://openalex.org/W4388798293","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"5R01GM065050-15","title":"Atomic-Resolution Analysis of Translation Control"},{"funder_name":"National Institutes of Health","grant_id":"1R35GM148352-01","title":"Mechanisms of Translation Control in Humans"},{"funder_name":"National Institutes of Health","grant_id":"5R35GM148352-03","title":"Mechanisms of Translation Control in Humans"},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM065050","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R35 GM148352","title":null}],"total_grants":5,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2024,"count":1}],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2023/11/17/2023.11.17.567602.full.pdf","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10680820","host_type":"GREEN"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2023/11/17/2023.11.17.567602.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2023.11.17.567602","host_type":"publisher"},{"url":"http://dx.doi.org/10.1101/2023.11.17.567602","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38014201","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10680820","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10680820/pdf/nihpp-2023.11.17.567602v1.pdf","host_type":"repository"},{"url":"https://doi.org/10.1101/2023.11.17.567602","host_type":""},{"url":"https://doi.org/10.1371/journal.pone.0299779","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/38483896","host_type":""},{"url":"http://dx.doi.org/10.1371/journal.pone.0299779","host_type":""},{"url":"https://doaj.org/article/b30386357de34fcc9fffdf0d0d4efcc9","host_type":""}],"fields_of_study":["RNA and protein synthesis mechanisms","RNA Research and Splicing","RNA regulation and disease","Medicine","Biology"],"mesh_terms":[],"keywords":["Five prime untranslated region","Eukaryotic translation","Start codon","Biology","Initiation factor","Untranslated region","Translation (biology)","Translational regulation","Upstream open reading frame","Messenger RNA","Internal ribosome entry site","EIF4E","Eukaryotic initiation factor","EIF4G","Ribosomal binding site","Genetics","Cell biology","Gene","Science","Eukaryotic Initiation Factor-3","Q","R","Codon, Initiator","Article","Protein Biosynthesis","Medicine","Animals","Humans","RNA, Messenger","5' Untranslated Regions","Research Article","Transcription Factors","5′ untranslated region","JUN mRNA","eukaryotic initiation factors","translation initiation"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-06T16:33:59.665601Z","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":[]}