{"doi":"10.1002/1873-3468.70122","title":"The 3′ end of the tale—neglected isoforms in cancer","abstract":"<jats:p>The evolutionary expansion of 3′ untranslated regions (3′UTRs), along with the incorporation of transposable elements and alternative polyadenylation (APA) sites, has introduced additional layers of gene expression control in eukaryotes. Consequently, 3′UTRs regulate the stability, translation, and localization of mRNAs by interacting with RNA‐binding proteins and non‐coding RNAs, thereby contributing to cell‐type‐specific and context‐dependent gene expression. Mounting evidence highlights the importance of non‐coding regions, particularly 3′UTRs, in normal physiology and disease states, including cancer. Genomic alterations and driver mutations in coding regions play a well‐established role in cancer biology. Advances in long‐read sequencing and 3′UTR‐focused genome‐/transcriptome‐wide association studies (GWAS/TWAS) improve our understanding of transcriptome complexity and how mRNA isoforms with different 3′‐ends may impact protein functions. This Review explores the regulatory roles of 3′UTRs, sources of 3′UTR isoform diversity, and implications in cancer, emphasizing the need for further research into their diagnostic and therapeutic potential.</jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"box\" position=\"anchor\">\n                      <jats:caption>\n                        <jats:title>Impact statement</jats:title>\n                      </jats:caption>\n                      <jats:p>This review highlights how alternative polyadenylation generates diverse mRNA 3′‐end isoforms in cancer. Isoforms with distinct 3′UTRs are differentially regulated by microRNAs and RNA‐binding proteins, while intronically polyadenylated isoforms can lead to C‐terminally truncated proteins with altered functions.</jats:p>\n                    </jats:boxed-text>\n                  </jats:p>","journal":"FEBS Letters","year":2025,"id":593461,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1518886,"name":"Ibrahim Ozgul","orcid":null,"position":1,"is_corresponding":false},{"id":732804,"name":"Ayşe Elif Erson-Bensan","orcid":"0000-0001-7398-9313","position":2,"is_corresponding":false},{"id":732800,"name":"Didem Naz Dioken","orcid":"0000-0001-8285-8147","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The 3′ end of the tale—neglected isoforms in cancer","abstract":"<jats:p>The evolutionary expansion of 3′ untranslated regions (3′UTRs), along with the incorporation of transposable elements and alternative polyadenylation (APA) sites, has introduced additional layers of gene expression control in eukaryotes. Consequently, 3′UTRs regulate the stability, translation, and localization of mRNAs by interacting with RNA‐binding proteins and non‐coding RNAs, thereby contributing to cell‐type‐specific and context‐dependent gene expression. Mounting evidence highlights the importance of non‐coding regions, particularly 3′UTRs, in normal physiology and disease states, including cancer. Genomic alterations and driver mutations in coding regions play a well‐established role in cancer biology. Advances in long‐read sequencing and 3′UTR‐focused genome‐/transcriptome‐wide association studies (GWAS/TWAS) improve our understanding of transcriptome complexity and how mRNA isoforms with different 3′‐ends may impact protein functions. This Review explores the regulatory roles of 3′UTRs, sources of 3′UTR isoform diversity, and implications in cancer, emphasizing the need for further research into their diagnostic and therapeutic potential.</jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"box\" position=\"anchor\">\n                      <jats:caption>\n                        <jats:title>Impact statement</jats:title>\n                      </jats:caption>\n                      <jats:p>This review highlights how alternative polyadenylation generates diverse mRNA 3′‐end isoforms in cancer. Isoforms with distinct 3′UTRs are differentially regulated by microRNAs and RNA‐binding proteins, while intronically polyadenylated isoforms can lead to C‐terminally truncated proteins with altered functions.</jats:p>\n                    </jats:boxed-text>\n                  </jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40696497","pmcid":null,"openalex_id":"https://openalex.org/W4412582140","authors":[],"funders":[{"funder_name":"Orta Doğu Teknik Üniversitesi","grant_id":"TEZ‐YL‐108‐2025‐11556","title":null},{"funder_name":"Orta Doğu Teknik Üniversitesi","grant_id":"TEZ‐YL‐108‐2022‐10886","title":null},{"funder_name":"Türkiye Bilimsel ve Teknolojik Araştırma Kurumu","grant_id":"119Z075","title":null},{"funder_name":"Türkiye Bilimsel ve Teknolojik Araştırma Kurumu","grant_id":"120Z464","title":null},{"funder_name":"Orta Doğu Teknik Üniversitesi","grant_id":"TEZ-YL-108-2025-11556","title":null},{"funder_name":"Orta Doğu Teknik Üniversitesi","grant_id":"TEZ-YL-108-2022-10886","title":null}],"total_grants":6,"fwci":0.8698,"citation_percentile":0.72614715,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1873-3468.70122","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1873-3468.70122","host_type":"publisher"},{"url":"https://febs.onlinelibrary.wiley.com/doi/pdf/10.1002/1873-3468.70122","host_type":"publisher"},{"url":"https://doi.org/10.1002/1873-3468.70122","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40696497","host_type":"repository"}],"fields_of_study":["RNA Research and Splicing","RNA modifications and cancer","RNA and protein synthesis mechanisms","Humans","Neoplasms","3' Untranslated Regions","Polyadenylation","RNA, Messenger","Gene Expression Regulation, Neoplastic","Animals","RNA Isoforms","Protein Isoforms"],"mesh_terms":["Animals","Humans","Neoplasms","RNA, Messenger","Gene Expression Regulation, Neoplastic","Protein Isoforms","3' Untranslated Regions","Polyadenylation","RNA Isoforms"],"keywords":["Polyadenylation","Biology","Gene isoform","Untranslated region","Three prime untranslated region","Computational biology","microRNA","Genetics","Post-transcriptional regulation","Transcriptome","Gene","Coding region","Regulation of gene expression","Gene expression","RNA","3′UTR","APA","cancer","isoform","mRNA","truncated protein"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T11:07:04.676826Z","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":[]}