{"doi":"10.1101/gad.342634.120","title":"The p53-induced RNA-binding protein ZMAT3 is a splicing regulator that inhibits the splicing of oncogenic CD44 variants in colorectal carcinoma","abstract":"p53 is an intensely studied tumor-suppressive transcription factor. Recent studies suggest that the RNA-binding protein (RBP) ZMAT3 is important in mediating the tumor-suppressive effects of p53. Here, we globally identify ZMAT3-regulated RNAs and their binding sites at nucleotide resolution in intact colorectal cancer (CRC) cells. ZMAT3 binds to thousands of mRNA precursors, mainly at intronic uridine-rich sequences and affects their splicing. The strongest alternatively spliced ZMAT3 target was CD44 , a cell adhesion gene and stem cell marker that controls tumorigenesis. Silencing ZMAT3 increased inclusion of CD44 variant exons, resulting in significant up-regulation of oncogenic CD44 isoforms ( CD44v ) and increased CRC cell growth that was rescued by concurrent knockdown of CD44v . Silencing p53 phenocopied the loss of ZMAT3 with respect to CD44 alternative splicing, suggesting that ZMAT3-mediated regulation of CD44 splicing is vital for p53 function. Collectively, our findings uncover a p53–ZMAT3–CD44 axis in growth suppression in CRC cells.","journal":"Genes & Development","year":2020,"id":118495,"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":70,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"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":328676,"name":"Dimitrios G. Anastasakis","orcid":"0000-0003-2306-275X","position":1,"is_corresponding":false},{"id":551478,"name":"Duncan Claypool","orcid":null,"position":2,"is_corresponding":false},{"id":232022,"name":"Lőrinc Sándor Pongor","orcid":"0000-0001-5917-4628","position":3,"is_corresponding":false},{"id":276769,"name":"Xiao Ling Li","orcid":null,"position":4,"is_corresponding":false},{"id":276007,"name":"Ioannis Grammatikakis","orcid":"0000-0002-8455-1584","position":5,"is_corresponding":false},{"id":550790,"name":"Minxue Liu","orcid":"0000-0002-7705-5822","position":6,"is_corresponding":false},{"id":550791,"name":"Xiantao Wang","orcid":"0000-0002-3383-2132","position":7,"is_corresponding":false},{"id":276013,"name":"Kannanganattu V. Prasanth","orcid":"0000-0003-4587-8362","position":8,"is_corresponding":false},{"id":241964,"name":"Mirit I. Aladjem","orcid":"0000-0002-1875-3110","position":9,"is_corresponding":false},{"id":256262,"name":"Ashish Lal","orcid":"0000-0002-4299-8177","position":10,"is_corresponding":false},{"id":246605,"name":"Markus Hafner","orcid":"0000-0002-4336-6518","position":11,"is_corresponding":false},{"id":276005,"name":"Bruna Rodrigues Muys","orcid":"0000-0002-3963-0865","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-18T23:13:58.531532Z","pmid":"33334821","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":[]}