{"doi":"10.1016/j.celrep.2024.114622","title":"RPL22 is a tumor suppressor in MSI-high cancers and a splicing regulator of MDM4","abstract":"Microsatellite instability-high (MSI-H) tumors are malignant tumors that, despite harboring a high mutational burden, often have intact TP53. One of the most frequent mutations in MSI-H tumors is a frameshift mutation in RPL22, a ribosomal protein. Here, we identified RPL22 as a modulator of MDM4 splicing through an alternative splicing switch in exon 6. RPL22 loss increases MDM4 exon 6 inclusion and cell proliferation and augments resistance to the MDM inhibitor Nutlin-3a. RPL22 represses the expression of its paralog, RPL22L1, by mediating the splicing of a cryptic exon corresponding to a truncated transcript. Therefore, damaging mutations in RPL22 drive oncogenic MDM4 induction and reveal a common splicing circuit in MSI-H tumors that may inform therapeutic targeting of the MDM4-p53 axis and oncogenic RPL22L1 induction.","journal":"Cell Reports","year":2024,"id":430217,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":75557,"name":"Kevin Hu","orcid":"0000-0002-3631-8294","position":1,"is_corresponding":false},{"id":315084,"name":"Lisa Fish","orcid":"0000-0001-9184-0512","position":2,"is_corresponding":false},{"id":1168720,"name":"Yih-An Chen","orcid":null,"position":3,"is_corresponding":false},{"id":842835,"name":"Paul Allegakoen","orcid":null,"position":4,"is_corresponding":false},{"id":1168722,"name":"Julia H. Pham","orcid":null,"position":5,"is_corresponding":false},{"id":1233654,"name":"Keliana S F Hui","orcid":null,"position":6,"is_corresponding":false},{"id":841789,"name":"Chih‐Hao Chang","orcid":"0000-0001-9794-0610","position":7,"is_corresponding":false},{"id":1233655,"name":"Meltem Tutar","orcid":null,"position":8,"is_corresponding":false},{"id":896899,"name":"Lorena Benitez-Rivera","orcid":null,"position":9,"is_corresponding":false},{"id":1168723,"name":"Maria B. Baco","orcid":null,"position":10,"is_corresponding":false},{"id":74108,"name":"Hanbing Song","orcid":"0000-0002-2164-8813","position":11,"is_corresponding":false},{"id":84954,"name":"Andrew O. Giacomelli","orcid":"0000-0003-2109-0458","position":12,"is_corresponding":false},{"id":58617,"name":"Francisca Vazquez","orcid":"0000-0002-2857-4685","position":13,"is_corresponding":false},{"id":58615,"name":"Mahmoud Ghandi","orcid":"0000-0003-1897-2265","position":14,"is_corresponding":false},{"id":43301,"name":"Hani Goodarzi","orcid":"0000-0002-9648-8949","position":15,"is_corresponding":false},{"id":36083,"name":"Franklin W. Huang","orcid":"0000-0001-5447-0436","position":16,"is_corresponding":false},{"id":74134,"name":"H Weinstein","orcid":"0000-0001-8409-4654","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T01:59:16.092672Z","pmid":"39146182","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":[]}