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- W4366241693 abstract "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." @default.
- W4366241693 created "2023-04-20" @default.
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- W4366241693 date "2023-04-18" @default.
- W4366241693 modified "2023-10-10" @default.
- W4366241693 title "Sex-lethal regulates back-splicing and generation of the sex-differentially expressed circular RNAs" @default.
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- W4366241693 doi "https://doi.org/10.1093/nar/gkad280" @default.
- W4366241693 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37070178" @default.
- W4366241693 hasPublicationYear "2023" @default.
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