{"doi":"10.1091/mbc.e08-10-1061","title":"Uncoupling Stress Granule Assembly and Translation Initiation Inhibition","abstract":"<jats:p> Cytoplasmic stress granules (SGs) are specialized regulatory sites of mRNA translation that form under different stress conditions known to inhibit translation initiation. The formation of SG occurs via two pathways; the eukaryotic initiation factor (eIF) 2α phosphorylation-dependent pathway mediated by stress and the eIF2α phosphorylation-independent pathway mediated by inactivation of the translation initiation factors eIF4A and eIF4G. In this study, we investigated the effects of targeting different translation initiation factors and steps in SG formation in HeLa cells. By depleting eIF2α, we demonstrate that reduced levels of the eIF2.GTP.Met-tRNAi<jats:sup>Met</jats:sup> ternary translation initiation complexes is sufficient to induce SGs. Likewise, reduced levels of eIF4B, eIF4H, or polyA-binding protein, also trigger SG formation. In contrast, depletion of the cap-binding protein eIF4E or preventing its assembly into eIF4F results in modest SG formation. Intriguingly, interfering with the last step of translation initiation by blocking the recruitment of 60S ribosome either with 2-(4-methyl-2,6-dinitroanilino)-N-methylpropionamideis or through depletion of the large ribosomal subunits protein L28 does not induce SG assembly. Our study identifies translation initiation steps and factors involved in SG formation as well as those that can be targeted without induction of SGs. </jats:p>","journal":"Molecular Biology of the Cell","year":2009,"id":21958,"datarank":7.21159257707557,"base_score":5.2832037287379885,"endowment":5.2832037287379885,"self_citation_contribution":0.7924805593106984,"citation_network_contribution":6.4191120177648715,"self_endowment_contribution":0.7924805593106984,"citer_contribution":6.4191120177648715,"corpus_percentile":null,"corpus_rank":null,"citation_count":196,"citer_count":190,"citers_with_citation_signal":168,"citers_with_endowment":168,"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":139556,"name":"John R. 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Kaufman","orcid":null,"position":6,"is_corresponding":false},{"id":137186,"name":"Jerry Pelletier","orcid":null,"position":7,"is_corresponding":false},{"id":139568,"name":"Rachid Mazroui","orcid":null,"position":8,"is_corresponding":false},{"id":139553,"name":"Sophie Mokas","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.2832037287379885,"endowment":5.2832037287379885,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19369421","pmcid":"PMC2688547","openalex_id":"https://openalex.org/W2102953537","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL052173","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"P01 HL057346","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R37 DK042394","title":null}],"total_grants":3,"fwci":5.2011,"citation_percentile":0.96352282,"influential_citations":9,"citation_trend":[{"year":2012,"count":10},{"year":2013,"count":16},{"year":2014,"count":9},{"year":2015,"count":11},{"year":2016,"count":14},{"year":2017,"count":6},{"year":2018,"count":5},{"year":2019,"count":10},{"year":2020,"count":16},{"year":2021,"count":20},{"year":2022,"count":16},{"year":2023,"count":12},{"year":2024,"count":12},{"year":2025,"count":11}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://europepmc.org/articles/pmc2688547?pdf=render","host_type":"GREEN"},{"url":"https://doi.org/10.1091/mbc.e08-10-1061","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19369421","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2688547","host_type":"repository"}],"fields_of_study":["RNA Research and Splicing","RNA regulation and disease","RNA and protein synthesis mechanisms","Biology","Medicine","Animals","Cell Line, Tumor","Cells, Cultured","Cytoplasmic Granules","Eukaryotic Initiation Factor-2","Eukaryotic Initiation Factor-4E","Eukaryotic Initiation Factors","Guanosine Triphosphate","HeLa Cells","Humans","Mice","Microscopy, Fluorescence","Peptide Chain Initiation, Translational","Phosphorylation","Poly(A)-Binding Proteins","Polyribosomes","Propionates","Protein Binding","Protein Biosynthesis","Protein Synthesis Inhibitors","RNA, Small Interfering","RNA, Transfer, Met","Ribosomes","Transfection"],"mesh_terms":["Animals","Cells, Cultured","Cytoplasmic Granules","Guanosine Triphosphate","HeLa Cells","Humans","Microscopy, Fluorescence","Peptide Chain Initiation, Translational","Phosphorylation","Polyribosomes","Propionates","Protein Binding","Protein Synthesis Inhibitors","Ribosomes","RNA, Transfer, Met","Transfection","Protein Biosynthesis","Eukaryotic Initiation Factor-2","RNA, Small Interfering","Poly(A)-Binding Proteins","Eukaryotic Initiation Factor-4E","Eukaryotic Initiation Factors","Cell Line, Tumor","Mice","Hela Cells"],"keywords":["EIF4G","Stress granule","EIF4E","Eukaryotic initiation factor","Initiation factor","Eukaryotic translation","Biology","eIF2","Internal ribosome entry site","EIF4A1","eIF4A","Cell biology","Translation (biology)","Eukaryotic Small Ribosomal Subunit","Protein biosynthesis","Eukaryotic translation initiation factor 4 gamma","EIF4EBP1","Integrated stress response","Messenger RNA","Molecular biology","Biochemistry","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-06T17:23:56.274385Z","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":[]}