{"doi":"10.1093/nar/gkad665","title":"TDP-1 and FUST-1 co-inhibit exon inclusion and control fertility together with transcriptional regulation","abstract":"Gene expression is a multistep process and crosstalk among regulatory layers plays an important role in coordinating gene expression. To identify functionally relevant gene expression coordination, we performed a systematic reverse-genetic interaction screen in C. elegans, combining RNA binding protein (RBP) and transcription factor (TF) mutants to generate over 100 RBP;TF double mutants. We identified many unexpected double mutant phenotypes, including two strong genetic interactions between the ALS-related RBPs, fust-1 and tdp-1, and the homeodomain TF ceh-14. Losing any one of these genes alone has no effect on the health of the organism. However, fust-1;ceh-14 and tdp-1;ceh-14 double mutants both exhibit strong temperature-sensitive fertility defects. Both double mutants exhibit defects in gonad morphology, sperm function, and oocyte function. RNA-Seq analysis of double mutants identifies ceh-14 as the main controller of transcript levels, while fust-1 and tdp-1 control splicing through a shared role in exon inhibition. A skipped exon in the polyglutamine-repeat protein pqn-41 is aberrantly included in tdp-1 mutants, and genetically forcing this exon to be skipped in tdp-1;ceh-14 double mutants rescues their fertility. Together our findings identify a novel shared physiological role for fust-1 and tdp-1 in promoting C. elegans fertility and a shared molecular role in exon inhibition.","journal":"Nucleic Acids Research","year":2023,"id":358665,"datarank":0.3897489378339882,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.01701294036578805,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.01701294036578805,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":3,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9615,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE230025"]},"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":691304,"name":"Olivia Marx","orcid":"0000-0001-9011-6127","position":1,"is_corresponding":false},{"id":691305,"name":"Adam Norris","orcid":"0000-0002-0570-7414","position":2,"is_corresponding":false},{"id":1007757,"name":"Morgan Taylor","orcid":"0000-0001-8280-0834","position":0,"is_corresponding":true}],"reference_count":99,"raw_metadata":null,"created_at":"2026-07-19T01:13:48.379546Z","pmid":"37587694","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":[]}