{"doi":"10.1101/2024.02.26.582126","title":"Biogenesis of circular RNAs <i>in vitro</i> and <i>in vivo</i> from the <i>Drosophila Nk2.1</i> / <i>scarecrow</i> gene","abstract":"Abstract scarecrow ( scro ) encodes a fly homolog of mammalian Nkx2.1 that is vital for early fly development as well as for optic lobe development. Interestingly, scro was reported to produce a circular RNA (circRNA). In this study, we identified 12 different scro circRNAs, which are either mono- or multi-exonic forms. The most abundant forms are circE2 carrying the second exon only and bi-exonic circE3-E4. Levels of circE2 show an age-dependent increase in adult heads, supporting a general trend of high accumulation of circRNAs in aged fly brains. Aligning sequences of introns flanking exons uncovered two pairs of intronic complementary sequences (ICSs); one pair residing in introns 1 and 2 and the other in introns 2 and 4. The first pair was demonstrated to be essential for the circE2 production in cell-based assays; furthermore, deletion of the region including potential ICS components in the intron-2 reduced in vivo production of circE2 and circE3-E4 by 80%, indicating them to be essential for the biogenesis of these isoforms. Besides the ICS, the intron regions immediately abutting exons seemed to be responsible for a basal level of circRNA formation. Moreover, the replacement of scro -ICS with those derived from laccase2 was comparably effective in scro -circRNA production, buttressing the importance of the hairpin-loop structure formed by ICS for the biogenesis of circRNA. Lastly, overexpressed scro affected outcomes of both linear and circular RNAs from the endogenous scro locus, suggesting that Scro plays a direct or indirect role in regulating expression levels of either or both forms.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":494817,"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":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1341171,"name":"Hyunjin Jeong","orcid":"0009-0000-0417-9763","position":1,"is_corresponding":false},{"id":370919,"name":"Gyunghee Lee","orcid":"0000-0003-3108-1870","position":2,"is_corresponding":false},{"id":370920,"name":"Jae H. Park","orcid":"0000-0002-4846-2197","position":3,"is_corresponding":false},{"id":422287,"name":"Siuk Yoo","orcid":"0000-0002-7787-1643","position":4,"is_corresponding":false},{"id":1341403,"name":"Suhyeon Son","orcid":null,"position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:09:11.736910Z","pmid":"38463984","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":[]}