{"doi":"10.1101/gr.156919.113","title":"3′ UTR-isoform choice has limited influence on the stability and translational efficiency of most mRNAs in mouse fibroblasts","abstract":"<jats:p>Variation in protein output across the genome is controlled at several levels, but the relative contributions of different regulatory mechanisms remain poorly understood. Here, we obtained global measurements of decay and translation rates for mRNAs with alternative 3′ untranslated regions (3′ UTRs) in murine 3T3 cells. Distal tandem isoforms had slightly but significantly lower mRNA stability and greater translational efficiency than proximal isoforms on average. The diversity of alternative 3′ UTRs also enabled inference and evaluation of both positively and negatively acting <jats:italic>cis</jats:italic>-regulatory elements. The 3′ UTR elements with the greatest implied influence were microRNA complementary sites, which were associated with repression of 32% and 4% at the stability and translational levels, respectively. Nonetheless, both the decay and translation rates were highly correlated for proximal and distal 3′ UTR isoforms from the same genes, implying that in 3T3 cells, alternative 3′ UTR sequences play a surprisingly small regulatory role compared to other mRNA regions.</jats:p>","journal":"Genome Research","year":2013,"id":21713,"datarank":8.147320319523576,"base_score":5.44673737166631,"endowment":5.44673737166631,"self_citation_contribution":0.8170106057499466,"citation_network_contribution":7.33030971377363,"self_endowment_contribution":0.8170106057499466,"citer_contribution":7.33030971377363,"corpus_percentile":null,"corpus_rank":null,"citation_count":231,"citer_count":200,"citers_with_citation_signal":187,"citers_with_endowment":187,"datacite_reuse_total":14,"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":42937,"name":"Christopher B. Burge","orcid":"0000-0001-9047-5648","position":1,"is_corresponding":false},{"id":59206,"name":"David P. Bartel","orcid":"0000-0002-3872-2856","position":2,"is_corresponding":false},{"id":138834,"name":"Noah Spies","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":14,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24072873","pmcid":"PMC3847777","openalex_id":"https://openalex.org/W2164440878","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM067031","title":null},{"funder_name":"NHGRI NIH HHS","grant_id":"T32 HG000044","title":null},{"funder_name":"NHGRI NIH HHS","grant_id":"R01 HG002439","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM085319","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM085319","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM067031","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM085319-07","title":"Function of Sequence-Specific Regulators of RNA Splicing"},{"funder_name":"National Institutes of Health","grant_id":"5R01GM067031-06","title":"MicroRNA genes and their functions"},{"funder_name":"Howard Hughes Medical Institute","grant_id":"","title":null},{"funder_name":"Howard Hughes Medical Institute","grant_id":"","title":null}],"total_grants":10,"fwci":null,"citation_percentile":null,"influential_citations":13,"citation_trend":[{"year":2013,"count":1},{"year":2014,"count":11},{"year":2015,"count":14},{"year":2016,"count":19},{"year":2017,"count":22},{"year":2018,"count":20},{"year":2019,"count":17},{"year":2020,"count":13},{"year":2021,"count":28},{"year":2022,"count":22},{"year":2023,"count":22},{"year":2024,"count":16},{"year":2025,"count":18},{"year":2026,"count":8}],"oa_status":"bronze","license":"CC BY NC","oa_locations":[{"url":"http://genome.cshlp.org/content/23/12/2078.full.pdf","host_type":"journal"},{"url":"http://genome.cshlp.org/content/23/12/2078.full.pdf","host_type":"HYBRID"},{"url":"http://genome.cshlp.org/content/23/12/2078.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1101/gr.156919.113","host_type":"publisher"},{"url":"https://doi.org/10.1101/gr.156919.113","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24072873","host_type":"repository"},{"url":"http://hdl.handle.net/1721.1/87993","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3847777","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC3847777","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC3847777?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1101/gr.156919.113","host_type":""},{"url":"https://dx.doi.org/10.1101/gr.156919.113","host_type":""},{"url":"https://orcid.org/0000-0002-3872-2856","host_type":""},{"url":"https://doi.org/https://doi.org/10.1101/gr.156919.113","host_type":""}],"fields_of_study":["RNA Research and Splicing","RNA and protein synthesis mechanisms","RNA modifications and cancer","Medicine","Biology","0301 basic medicine","0303 health sciences","03 medical and health sciences","3' Untranslated Regions","3T3 Cells","Alternative Splicing","Animals","Fibroblasts","Gene Expression Regulation","Genome","Linear Models","Mice","MicroRNAs","Molecular Conformation","Nucleotide Motifs","Open Reading Frames","Polyadenylation","Protein Biosynthesis","RNA Isoforms","RNA Stability","RNA, Messenger","Regulatory Elements, Transcriptional","Sequence Analysis, RNA"],"mesh_terms":["Animals","Fibroblasts","Gene Expression Regulation","Molecular Conformation","RNA, Messenger","Protein Biosynthesis","Linear Models","Open Reading Frames","3T3 Cells","Genome","Alternative Splicing","Sequence Analysis, RNA","3' Untranslated Regions","RNA Stability","Polyadenylation","MicroRNAs","Regulatory Elements, Transcriptional","Mice","RNA Isoforms","Nucleotide Motifs"],"keywords":["Gene isoform","Biology","Translational efficiency","Untranslated region","Three prime untranslated region","Translation (biology)","Translational regulation","Five prime untranslated region","microRNA","Messenger RNA","Post-translational regulation","AU-rich element","Eukaryotic translation","Genetics","Cell biology","Gene","Molecular biology","Genome","Sequence Analysis, RNA","Research","RNA Stability","Molecular Conformation","3T3 Cells","Fibroblasts","Polyadenylation","Alternative Splicing","Mice","MicroRNAs","Open Reading Frames","Gene Expression Regulation","Protein Biosynthesis","Linear Models","RNA Isoforms","Animals","RNA, Messenger","Regulatory Elements, Transcriptional","Nucleotide Motifs","3' Untranslated Regions"],"sdg_mappings":[],"linked_datasets":[{"doi":"10.6084/m9.figshare.14037341.v1","title":"Additional file 1 of Characterizing RNA stability genome-wide through combined analysis of PRO-seq and RNA-seq 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