{"doi":"10.1101/2023.07.26.550700","title":"Orb2 enables rare-codon-enriched mRNA expression during <i>Drosophila</i> neuron differentiation","abstract":"Abstract Regulation of codon optimality is an increasingly appreciated layer of cell- and tissue-specific protein expression control. Here, we use codon-modified reporters to show that differentiation of Drosophila neural stem cells into neurons enables protein expression from rare-codon-enriched genes. From a candidate screen, we identify the cytoplasmic polyadenylation element binding (CPEB) protein Orb2 as a positive regulator of rare-codon-dependent expression in neurons. Using RNA sequencing, we reveal that Orb2-upregulated mRNAs in the brain with abundant Orb2 binding sites have a rare-codon bias. From these Orb2-regulated mRNAs, we demonstrate that rare-codon enrichment is important for expression control and social behavior function of the metabotropic glutamate receptor (mGluR). Our findings reveal a molecular mechanism by which neural stem cell differentiation shifts genetic code regulation to enable critical mRNA and protein expression.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":409864,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"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":1189733,"name":"Patrick Viet-Quoc Nguyen","orcid":"0000-0001-6358-5948","position":1,"is_corresponding":false},{"id":45256,"name":"Alain Laederach","orcid":"0000-0002-5088-9907","position":2,"is_corresponding":false},{"id":989129,"name":"Pelin Volkan","orcid":"0000-0002-0001-0626","position":3,"is_corresponding":false},{"id":386003,"name":"Jessica K. Sawyer","orcid":"0000-0001-9026-0559","position":4,"is_corresponding":false},{"id":239756,"name":"Donald T. Fox","orcid":"0000-0002-0436-179X","position":5,"is_corresponding":false},{"id":386767,"name":"Rebeccah K. Stewart","orcid":null,"position":0,"is_corresponding":true}],"reference_count":134,"raw_metadata":null,"created_at":"2026-07-19T01:21:31.144858Z","pmid":"37546801","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":[]}