biostudies-literatureLiu DNational Health and Medical Research Council of AustraliaNSERCNational Science and Engineering Research Council of CanadaRoyal Adelaide Hospital Florey FellowshipNational Natural Science Foundation of ChinaUniversity of South AustraliaNCI NIH HHSGuangdong Science and Technology DepartmentNational Breast Cancer FoundationCanada Research Chair in Functional Proteomics1387-1403https://www.ebi.ac.uk/biostudies/studies/S-EPMC10853802biostudies-literatureUnknown52(3)While the majority of circRNAs are formed from infrequent back-splicing of exons from protein coding genes, some can be produced at quite high level and in a regulated manner. We describe the regulation, biogenesis and function of circDOCK1(2-27), a large, abundant circular RNA that is highly regulated during epithelial-mesenchymal transition (EMT) and whose formation depends on the epithelial splicing regulator ESRP1. CircDOCK1(2-27) synthesis in epithelial cells represses cell motility both by diverting transcripts from DOCK1 mRNA production to circRNA formation and by direct inhibition of migration by the circRNA. HITS-CLIP analysis and CRISPR-mediated deletions indicate ESRP1 controls circDOCK1(2-27) biosynthesis by binding a GGU-containing repeat region in intron 1 and detaining its sNucleic acids researchESRP1 controls biogenesis and function of a large abundant multiexon circRNA.PMC10853802GNT1118170GNT1089167RGPIN-2019-06297P30 CA0087482020B1212030004319004352020B1212060018IN-16-072Dyakov BJAPatel DGuo WConn VMConn SJWu BGregory PABert AGMigault MMDredge BKToubia JGoodall GJPillman KALiu DGingras ACfalseESRP1 controls biogenesis and function of a large abundant multiexon circRNA.While the majority of circRNAs are formed from infrequent back-splicing of exons from protein coding genes, some can be produced at quite high level and in a regulated manner. We describe the regulation, biogenesis and function of circDOCK1(2-27), a large, abundant circular RNA that is highly regulated during epithelial-mesenchymal transition (EMT) and whose formation depends on the epithelial splicing regulator ESRP1. CircDOCK1(2-27) synthesis in epithelial cells represses cell motility both by diverting transcripts from DOCK1 mRNA production to circRNA formation and by direct inhibition of migration by the circRNA. HITS-CLIP analysis and CRISPR-mediated deletions indicate ESRP1 controls circDOCK1(2-27) biosynthesis by binding a GGU-containing repeat region in intron 1 and detaining its s2024-01-01T00:00:00Z2024 Feb2026-05-01T03:23:18.964Z2025-04-05T14:51:12.646ZS-EPMC108538023801546810.1093/nar/gkad1138