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Sex-lethal regulates back-splicing and generation of the sex-differentially expressed circular RNAs

ABSTRACT: Sex-lethal regulates back-splicing and generation of the sex-differentially expressed circular RNAs

PROVIDER: PRJNA912753 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22757300_1.fastq.gz	Fastqsanger.gz
	SRR22757300_2.fastq.gz	Fastqsanger.gz
	SRR22757301_1.fastq.gz	Fastqsanger.gz
	SRR22757301_2.fastq.gz	Fastqsanger.gz
	SRR22757302.fastq.gz	Fastqsanger.gz

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Similar Datasets

Sex-lethal regulates back-splicing and generation of the sex-differentially expressed circular RNAs

Project description:Conversely to canonical splicing, back-splicing covalently ligates the upstream 3' splice site (SS) with downstream 5'SS and generates exonic circular RNAs (circRNAs) that are widely-identified in eukaryotes and have regulatory functions in gene expression. However, sex-specific back-splicing in Drosophila has not been investigated and its regulation remains unclear. Here, we performed multiple RNA-seq of various sex-specific Drosophila samples including head, body and gonads from both genders, and identified more than ten thousand of circular RNAs, in which hundreds are sex-differentially expressed and back-spliced. Intriguingly, we found that expression of SXL, an RNA-binding protein encoded by Sex-lethal (Sxl), the master Drosophila sex-determination gene which only functionally spliced in females, promotes back-splicing of many female-differentially expressed circRNAs in the male S2 cells, while expression of a SXL mutant did not. Using a monoclonal antibody, we further obtained the transcriptome-wide RNA-binding sites of SXL through a PAR-CLIP approach and revealed that SXL-binding on flanking exons and introns of pre-mRNAs facilitates back-splicing of those circRNAs, whereas SXL-binding on the circRNA exons inhibits the back-splicing. This study provides strong evidence that SXL has a regulatory role in back-splicing to generate sex-specifc circRNAs, as well as in the initiation of Drosophila sex-determination cascade through canoncial forward-splicing.

2023-04-23 | GSE221102 | GEO

Sex-lethal regulates back-splicing and generation of the sex-differentially expressed circular RNAs.

Project description: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.

| S-EPMC10250224 | biostudies-literature

Back-splice junctions of KSHV circular RNAs

Project description:Back-splice junctions of KSHV circular RNAs

| PRJNA694907 | ENA

seekCRIT: detecting and characterizing differentially expressed circular RNAs using high-throughput sequencing data

Project description:Recently, it has been demonstrated that genomes of many species express single stranded RNAs with covalently closed ends, named circular RNAs. Their regulatory potential and functional relevance are just starting to be revealed. Here we present a novel computational tool, seekCRIT (seek for differentially expressed Circular RNAs In Transcriptome), that identifies circular RNAs and detects their differential expression between two conditions. Using seekCRIT we identified the circular RNAs that are expressed in the neural retina and determined that the majority of them (74%) are expressed in both, ischemic and normal conditions. We identified over 40 circular RNAs that were differentially expressed between both conditions and validated these experimentally using qRT-PCR. The high validation rate of 90% with a false discovery rate (FDR) of < 5% demonstrates the accuracy and reliability of seekCRIT.

2021-02-02 | GSE114896 | GEO

The differentially expressed circular RNAs in the hippocampus of Nrf2-knockout mice

Project description:Non-coding circular RNAs (circRNAs) have displayed dysregulated expression in the hippocampus of Nrf2-knockout mice.

2019-08-22 | GSE122421 | GEO

Back-spliced RNA from Retrotransposon Binds to Centromere and Regulates Centromeric Chromatin Loops in Maize

Project description:In most plants, centromeric DNA contains highly repetitive sequences, including tandem repeats and retrotransposons; however, the roles of these sequences in the structure and function of the centromere are unclear. Here, we found that retrotransposon-derived back-spliced RNA can bind to the centromere through R-loops and regulate the formation of centromeric chromatin loops. Multiple RNA sequences from centromeric retrotransposons (CRMs) were enriched in maize (Zea mays) centromeres and back spliced RNA from CRM1 were detected. We identified three types of circular CRM1 RNAs with the same back-splicing site based on the back-spliced sequences. These circular RNAs bound to the centromere through R-loops. Two R-loop sites inside a single circular RNA promoted the formation of chromatin loops in CRM1 regions. When RNAi was used to target the back-spliced site of the circular CRM1 RNAs, the levels of R-loops and chromatin loops formed by these circular RNAs decreased, while the levels of R-loops produced by linear RNAs with similar binding sites increased. Linear RNAs with only one R-loop site could not promote chromatin loop formation. Higher levels of R-loops and lower levels of chromatin loops in the CRM1 regions of RNAi plants led to a reduced localization of the centromeric H3 variant (CENH3). Our work reveals that centromeric chromatin organization by circular CRM1 RNAs via R-loops and chromatin loops. R-loops are integral components of centromeric chromatin. Proper centromere structure is essential for CENH3 localization. CRM1 elements may have helped to build a suitable chromatin environment during centromere evolution.

2020-01-01 | GSE137701 | GEO

The Nab2 RNA binding protein promotes sex-specific splicing of Sex lethal in Drosophila neuronal tissue

Project description:The Nab2 RNA binding protein promotes sex-specific splicing of Sex lethal in Drosophila neuronal tissue

| PRJNA682171 | ENA

Flipping the switch on Sex-lethal expression: Sister of Sex-lethal antagonizes Sxl-dependent alternative splicing to maintain a male-specific gene expression pattern in Drosophila (iCLIP)

Project description:In Drosophila female development is governed by a single RNA-binding protein, Sex lethal (Sxl), that controls the expression of key factors involved in dosage compensation, germline homeostasis and the establishment of female morphology and behaviour. Functional Sxl protein is only synthesized in female flies. Its expression is established in the pre-cellular, female embryo by an X-chromosome counting mechanism and maintained by a positive feedback loop with Sxl controlling alternative splicing of its own transcript. In male flies this feedback loop is not activated, keeping Sxl expression in the ‘off’ state. But what protects males against accidental triggering of the self-sustaining feedback loop and Sxl protein production snowballing out of control? Here we identify Sister of sex lethal (Ssx) as a protein that antagonizes Sxl in autoregulatory splicing by competition for the same RNA elements. Male flies mutant for ssx exhibit a low level of productive Sxl mRNA splicing and in cultured Drosophila cells, Sxl-induced changes in alternative splicing can be reverted by the expression of Ssx. In sum, this demonstrates that Ssx helps to establish a stable, male-specific gene expression pattern by protecting male flies against triggering Sxl expression.

2019-01-15 | GSE98188 | GEO

Flipping the switch on Sex-lethal expression: Sister of Sex-lethal antagonizes Sxl-dependent alternative splicing to maintain a male-specific gene expression pattern in Drosophila (RIP-Seq)

2019-01-15 | GSE98187 | GEO

Flipping the switch on Sex-lethal expression: Sister of Sex-lethal antagonizes Sxl-dependent alternative splicing to maintain a male-specific gene expression pattern in Drosophila

Project description:Flipping the switch on Sex-lethal expression: Sister of Sex-lethal antagonizes Sxl-dependent alternative splicing to maintain a male-specific gene expression pattern in Drosophila

| PRJNA384219 | ENA

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