{"doi":"10.1093/nar/gkaa491","title":"Activation and inhibition of nonsense-mediated mRNA decay control the abundance of alternative polyadenylation products","abstract":"Alternative polyadenylation (APA) produces transcript 3' untranslated regions (3'UTRs) with distinct sequences, lengths, stabilities and functions. We show here that APA products include a class of cryptic nonsense-mediated mRNA decay (NMD) substrates with extended 3'UTRs that gene- or transcript-level analyses of NMD often fail to detect. Transcriptome-wide, the core NMD factor UPF1 preferentially recognizes long 3'UTR products of APA, leading to their systematic downregulation. Counteracting this mechanism, the multifunctional RNA-binding protein PTBP1 regulates the balance of short and long 3'UTR isoforms by inhibiting NMD, in addition to its previously described modulation of co-transcriptional polyadenylation (polyA) site choice. Further, we find that many transcripts with altered APA isoform abundance across multiple tumor types are controlled by NMD. Together, our findings reveal a widespread role for NMD in shaping the outcomes of APA.","journal":"Nucleic Acids Research","year":2020,"id":101577,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":498324,"name":"Sarah E Fritz","orcid":null,"position":1,"is_corresponding":false},{"id":497232,"name":"Nazmul Haque","orcid":"0000-0001-8950-929X","position":2,"is_corresponding":false},{"id":498325,"name":"Zhiyun Ge","orcid":null,"position":3,"is_corresponding":false},{"id":421967,"name":"Ilker Tunc","orcid":"0000-0001-5699-7549","position":4,"is_corresponding":false},{"id":107264,"name":"Wenjing Yang","orcid":"0000-0003-1541-1892","position":5,"is_corresponding":false},{"id":373441,"name":"Jun Zhu","orcid":"0000-0003-4573-8933","position":6,"is_corresponding":false},{"id":348289,"name":"J. Robert Hogg","orcid":"0000-0001-5729-5135","position":7,"is_corresponding":false},{"id":497231,"name":"Aparna Kishor","orcid":"0000-0003-0212-7614","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T22:40:22.678835Z","pmid":"32542372","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":[]}