{"doi":"10.1126/science.1144467","title":"Cap-Independent Translation Is Required for Starvation-Induced Differentiation in Yeast","abstract":"<jats:p>Cellular internal ribosome entry sites (IRESs) are untranslated segments of mRNA transcripts thought to initiate protein synthesis in response to environmental stresses that prevent canonical 5′ cap–dependent translation. Although numerous cellular mRNAs are proposed to have IRESs, none has a demonstrated physiological function or molecular mechanism. Here we show that seven yeast genes required for invasive growth, a developmental pathway induced by nutrient limitation, contain potent IRESs that require the initiation factor eIF4G for cap-independent translation. In contrast to the RNA structure-based activity of viral IRESs, we show that an unstructured A-rich element mediates internal initiation via recruitment of the poly(A) binding protein (Pab1) to the 5′ untranslated region (UTR) of invasive growth messages. A 5′UTR mutation that impairs IRES activity compromises invasive growth, which indicates that cap-independent translation is required for physiological adaptation to stress.</jats:p>","journal":"Science","year":2007,"id":21619,"datarank":8.666517004153322,"base_score":5.44673737166631,"endowment":5.44673737166631,"self_citation_contribution":0.8170106057499466,"citation_network_contribution":7.849506398403376,"self_endowment_contribution":0.8170106057499466,"citer_contribution":7.849506398403376,"corpus_percentile":null,"corpus_rank":null,"citation_count":231,"citer_count":200,"citers_with_citation_signal":188,"citers_with_endowment":188,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":138503,"name":"Kaihong Zhou","orcid":null,"position":1,"is_corresponding":false},{"id":138504,"name":"Tamira K. Butler","orcid":null,"position":2,"is_corresponding":false},{"id":2407,"name":"Jennifer A. Doudna","orcid":"0000-0001-9161-999X","position":3,"is_corresponding":false},{"id":138500,"name":"Wendy V. Gilbert","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.44673737166631,"endowment":5.44673737166631,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17761883","pmcid":null,"openalex_id":"https://openalex.org/W2004143350","authors":[],"funders":[],"total_grants":0,"fwci":6.7269,"citation_percentile":0.97692099,"influential_citations":16,"citation_trend":[{"year":2012,"count":15},{"year":2013,"count":7},{"year":2014,"count":8},{"year":2015,"count":11},{"year":2016,"count":12},{"year":2017,"count":15},{"year":2018,"count":16},{"year":2019,"count":8},{"year":2020,"count":17},{"year":2021,"count":11},{"year":2022,"count":7},{"year":2023,"count":14},{"year":2024,"count":15},{"year":2025,"count":7},{"year":2026,"count":2}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.science.org/doi/pdf/10.1126/science.1144467","host_type":"publisher"},{"url":"https://doi.org/10.1126/science.1144467","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17761883","host_type":"repository"}],"fields_of_study":["RNA and protein synthesis mechanisms","RNA Research and Splicing","Viral Infections and Immunology Research","Biology","Medicine","5' Untranslated Regions","Adaptation, Physiological","Eukaryotic Initiation Factor-4G","Genes, Fungal","Glucose","Nuclear Proteins","Nucleic Acid Conformation","Peptide Chain Initiation, Translational","Poly A","Poly(A)-Binding Proteins","Protein Biosynthesis","RNA Caps","RNA, Fungal","RNA, Messenger","Saccharomyces cerevisiae","Saccharomyces cerevisiae Proteins","Trans-Activators"],"mesh_terms":["Adaptation, Physiological","Genes, Fungal","Glucose","Nuclear Proteins","Nucleic Acid Conformation","Peptide Chain Initiation, Translational","Poly A","RNA Caps","RNA, Fungal","RNA, Messenger","Saccharomyces cerevisiae","Protein Biosynthesis","Trans-Activators","5' Untranslated Regions","Saccharomyces cerevisiae Proteins","Poly(A)-Binding Proteins","Eukaryotic Initiation Factor-4G"],"keywords":["Internal ribosome entry site","EIF4G","Five prime untranslated region","Translation (biology)","Eukaryotic initiation factor","Three prime untranslated region","Untranslated region","Cell biology","EIF4E","Biology","Eukaryotic translation","Stress granule","EIF4A1","Initiation factor","Integrated stress response","Eukaryotic translation initiation factor 4 gamma","Translational regulation","RNA-binding protein","Genetics","Messenger RNA","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-06T16:23:36.993228Z","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,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}