{"doi":"10.1371/journal.pbio.3002028","title":"TDP-43 and other hnRNPs regulate cryptic exon inclusion of a key ALS/FTD risk gene, UNC13A","abstract":"A major function of TAR DNA-binding protein-43 (TDP-43) is to repress the inclusion of cryptic exons during RNA splicing. One of these cryptic exons is in UNC13A, a genetic risk factor for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The accumulation of cryptic UNC13A in disease is heightened by the presence of a risk haplotype located within the cryptic exon itself. Here, we revealed that TDP-43 extreme N-terminus is important to repress UNC13A cryptic exon inclusion. Further, we found hnRNP L, hnRNP A1, and hnRNP A2B1 bind UNC13A RNA and repress cryptic exon inclusion, independently of TDP-43. Finally, higher levels of hnRNP L protein associate with lower burden of UNC13A cryptic RNA in ALS/FTD brains. Our findings suggest that while TDP-43 is the main repressor of UNC13A cryptic exon inclusion, other hnRNPs contribute to its regulation and may potentially function as disease modifiers.","journal":"PLoS Biology","year":2023,"id":317613,"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":75,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":238157,"name":"Sarah Pickles","orcid":"0000-0001-7956-4586","position":1,"is_corresponding":false},{"id":1024646,"name":"Virginia Estades Ayuso","orcid":null,"position":2,"is_corresponding":false},{"id":238164,"name":"Karen Jansen‐West","orcid":"0000-0002-1234-7103","position":3,"is_corresponding":false},{"id":567365,"name":"Yue Qi","orcid":"0000-0003-1914-8710","position":4,"is_corresponding":false},{"id":325475,"name":"Ziyi Li","orcid":"0000-0002-5165-8772","position":5,"is_corresponding":false},{"id":238163,"name":"Lillian M. Daughrity","orcid":"0000-0003-4644-7265","position":6,"is_corresponding":false},{"id":239293,"name":"Mei Yue","orcid":null,"position":7,"is_corresponding":false},{"id":241295,"name":"Yong‐Jie Zhang","orcid":"0000-0002-9900-4313","position":8,"is_corresponding":false},{"id":228615,"name":"Casey Cook","orcid":"0000-0002-5963-8442","position":9,"is_corresponding":false},{"id":54753,"name":"Dennis W. Dickson","orcid":"0000-0001-7189-7917","position":10,"is_corresponding":false},{"id":225567,"name":"Michael E. Ward","orcid":"0000-0002-5296-8051","position":11,"is_corresponding":false},{"id":228616,"name":"Leonard Petrucelli","orcid":"0000-0003-2959-129X","position":12,"is_corresponding":false},{"id":238155,"name":"Mercedes Prudencio","orcid":"0000-0002-4894-4858","position":13,"is_corresponding":false},{"id":805534,"name":"Yuka Koike","orcid":"0000-0002-5067-8579","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:06:55.884740Z","pmid":"36930682","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":[]}