{"doi":"10.1073/pnas.96.23.13118","title":"Identification of eukaryotic mRNAs that are translated at reduced cap binding complex eIF4F concentrations using a cDNA microarray","abstract":"<jats:p>Although most eukaryotic mRNAs need a functional cap binding complex eIF4F for efficient 5′ end- dependent scanning to initiate translation, picornaviral, hepatitis C viral, and a few cellular RNAs have been shown to be translated by internal ribosome entry, a mechanism that can operate in the presence of low levels of functional eIF4F. To identify cellular mRNAs that can be translated when eIF4F is depleted or in low abundance and that, therefore, may contain internal ribosome entry sites, mRNAs that remained associated with polysomes were isolated from human cells after infection with poliovirus and were identified by using a cDNA microarray. Approximately 200 of the 7000 mRNAs analyzed remained associated with polysomes under these conditions. Among the gene products encoded by these polysome-associated mRNAs were immediate-early transcription factors, kinases, and phosphatases of the mitogen-activated protein kinase pathways and several protooncogenes, including c-myc and Pim-1. In addition, the mRNA encoding Cyr61, a secreted factor that can promote angiogenesis and tumor growth, was selectively mobilized into polysomes when eIF4F concentrations were reduced, although its overall abundance changed only slightly. Subsequent tests confirmed the presence of internal ribosome entry sites in the 5′ noncoding regions of both Cyr61 and Pim-1 mRNAs. Overall, this study suggests that diverse mRNAs whose gene products have been implicated in a variety of stress responses, including inflammation, angiogenesis, and the response to serum, can use translational initiation mechanisms that require little or no intact cap binding protein complex eIF4F.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":1999,"id":21024,"datarank":13.919744871276256,"base_score":5.961005339623274,"endowment":5.961005339623274,"self_citation_contribution":0.8941508009434912,"citation_network_contribution":13.025594070332765,"self_endowment_contribution":0.8941508009434912,"citer_contribution":13.025594070332765,"corpus_percentile":null,"corpus_rank":null,"citation_count":387,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":2,"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":136927,"name":"Mark S. Carter","orcid":null,"position":1,"is_corresponding":false},{"id":35665,"name":"Michael B. Eisen","orcid":"0000-0002-7528-738X","position":2,"is_corresponding":false},{"id":35687,"name":"Patrick O. Brown","orcid":"0000-0002-9940-5993","position":3,"is_corresponding":false},{"id":136928,"name":"Peter Sarnow","orcid":null,"position":4,"is_corresponding":false},{"id":136926,"name":"Gregg Johannes","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.961005339623274,"endowment":5.961005339623274,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10557283","pmcid":"PMC23910","openalex_id":"https://openalex.org/W2021263359","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"F32 GM16751","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM055979","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM55979","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"F32 GM016751","title":null}],"total_grants":4,"fwci":14.3312,"citation_percentile":0.99462405,"influential_citations":14,"citation_trend":[{"year":2012,"count":21},{"year":2013,"count":11},{"year":2014,"count":21},{"year":2015,"count":11},{"year":2016,"count":12},{"year":2017,"count":5},{"year":2018,"count":12},{"year":2019,"count":9},{"year":2020,"count":9},{"year":2021,"count":6},{"year":2022,"count":5},{"year":2023,"count":4},{"year":2024,"count":2},{"year":2025,"count":6}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://europepmc.org/articles/pmc23910?pdf=render","host_type":"GREEN"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.96.23.13118","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.96.23.13118","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10557283","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/23910","host_type":"repository"}],"fields_of_study":["Cancer Mechanisms and Therapy","Cytokine Signaling Pathways and Interactions","interferon and immune responses","Biology","Medicine","Cysteine-Rich Protein 61","DNA, Complementary","Growth Substances","HeLa Cells","Humans","Immediate-Early Proteins","Intercellular Signaling Peptides and Proteins","Nucleic Acid Hybridization","Poliovirus","Protein Biosynthesis","Protein Serine-Threonine Kinases","Proto-Oncogene Proteins","Proto-Oncogene Proteins c-pim-1","RNA Caps","RNA, Messenger"],"mesh_terms":["Growth Substances","HeLa Cells","Humans","Nucleic Acid Hybridization","Proto-Oncogene Proteins","RNA Caps","RNA, Messenger","Protein Biosynthesis","Protein Serine-Threonine Kinases","Immediate-Early Proteins","Poliovirus","DNA, Complementary","Intercellular Signaling Peptides and Proteins","Proto-Oncogene Proteins c-pim-1","Cysteine-Rich Protein 61","Hela Cells"],"keywords":["Polysome","Biology","EIF4E","Translational efficiency","Internal ribosome entry site","Eukaryotic initiation factor","Gene expression","Messenger RNA","Translational regulation","Cell biology","Translation (biology)","Ribosomal binding site","Protein biosynthesis","Molecular biology","RNA","Gene","Ribosome","Genetics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.12947656.v1","title":"Additional file 1 of Expression of ACE2 and a viral virulence-regulating factor CCN family member 1 in human iPSC-derived neural cells: implications for COVID-19-related CNS disorders","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.12947656","title":"Additional file 1 of Expression of ACE2 and a viral virulence-regulating factor CCN family member 1 in human iPSC-derived neural cells: implications for COVID-19-related CNS disorders","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-06T14:07:44.016097Z","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":[]}