ArticleNucleic acids research2023
Sex-lethal regulates back-splicing and generation of the sex-differentially expressed circular RNAs.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- A framework for identifying transcript orthologs: the evolution of sex bias in alternative transcript structure in Drosophila.bioRxiv : the preprint server for biology · 2026Article
- Molecular mechanisms and clinical impacts of sex differences in urologic cancers.Discover oncology · 2026Review
- An ultraconserved pseudo 5' splice site fine-tunes development by regulating alternative splicing within TOR-related pathways.Nature communications · 2026Article
- Molecular Characteristics, Circularization Mechanism, and Potential Functions of circRNA-0172.Genes · 2025Article
- Functional regulatory mechanisms of circRNAs in bovine adipogenesis.Cytotechnology · 2025Review
- FUS Selectively Facilitates circRNAs Packing into Small Extracellular Vesicles within Hypoxia Neuron.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- RNA-Binding Proteins (RBPs) and Circular RNA Biogenesis.Advances in experimental medicine and biology · 2025Review
- The role of circular RNA in immune response to tuberculosis and its potential as a biomarker and therapeutic target.Frontiers in immunology · 2025Review
- Conserved intronic secondary structures with concealed branch sites regulate alternative splicing of poison exons.Nucleic acids research · 2024Article
- Signature and function of plasma exosome-derived circular RNAs in patients with hypertensive intracerebral hemorrhage.Molecular genetics and genomics : MGG · 2024Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Conversely to canonical splicing, back-splicing connects the upstream 3' splice site (SS) with a downstream 5'SS and generates exonic circular RNAs (circRNAs) that are widely identified and have regulatory functions in eukaryotic gene expression. However, sex-specific back-splicing in Drosophila has not been investigated and its regulation remains unclear. Here, we performed multiple RNA analyses of a variety sex-specific Drosophila samples and identified over ten thousand circular RNAs, in which hundreds are sex-differentially and -specifically back-spliced. Intriguingly, we found that expression of SXL, an RNA-binding protein encoded by Sex-lethal (Sxl), the master Drosophila sex-determination gene that is only spliced into functional proteins in females, promoted back-splicing of many female-differential circRNAs in the male S2 cells, whereas expression of a SXL mutant (SXLRRM) did not promote those events. Using a monoclonal antibody, we further obtained the transcriptome-wide RNA-binding sites of SXL through PAR-CLIP. After splicing assay of mini-genes with mutations in the SXL-binding sites, we revealed that SXL-binding on flanking exons and introns of pre-mRNAs facilitates back-splicing, whereas SXL-binding on the circRNA exons inhibits back-splicing. This study provides strong evidence that SXL has a regulatory role in back-splicing to generate sex-specific and -differential circRNAs, as well as in the initiation of sex-determination cascade through canonical forward-splicing.
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