{"doi":"10.1093/nar/gkaf785","title":"The kinase GSK-3 alters the RNA-binding protein landscape of lipid metabolism transcripts leading to altered expression in the <i>C. elegans</i> nervous system","abstract":"Tissue-specific regulation of gene expression is essential for multicellular organisms, and RNA-binding proteins play central roles in these molecular processes. To determine how the Caenorhabditis elegans RNA-binding protein, ADR-1, regulates tissue-specific gene expression, we profiled the RNA-binding targets of ADR-1 in neural cells and assessed the effects of ADR-1 binding on neural gene expression. We identified a cohort of neural transcripts that function in lipid metabolism and are directly regulated by ADR-1 binding. To identify cellular factors that influence ADR-1 binding, a forward genetic screen was performed, revealing that the serine/threonine protein kinase, glycogen synthase kinase-3 (GSK-3), inhibits ADR-1 binding to the cohort. Further investigation revealed that the RNA-binding protein VIG-1 physically interacts with ADR-1, and the two proteins coordinately bind the neural lipid metabolism transcripts. Additional experiments revealed that VIG-1 is phosphorylated in a GSK-3-dependent manner, which inhibits the VIG-1-ADR-1 complex from binding the regulon in wild-type animals. Importantly, inhibition of GSK-3 kinase activity in wild-type animals also resulted in decreased neural expression of lipid metabolism genes. Together, we reveal that the interplay between a kinase and RNA-binding proteins regulates the expression of lipid metabolism genes within neural cells, potentially impacting stress resistance and longevity.","journal":"Nucleic Acids Research","year":2025,"id":553888,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1451231,"name":"Meghana Mohankumar","orcid":null,"position":1,"is_corresponding":false},{"id":312032,"name":"Heather A. Hundley","orcid":"0000-0002-9106-9016","position":2,"is_corresponding":false},{"id":312029,"name":"Ananya Mahapatra","orcid":"0000-0003-1050-1899","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T02:54:45.872391Z","pmid":"40829802","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":[]}