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Rbfox contributes to a conservative program of self-antigen splicing in thymic epithelial cells

ABSTRACT: Rbfox contributes to a conservative program of self-antigen splicing in thymic epithelial cells

PROVIDER: PRJNA608751 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11182044_1.fastq.gz	Fastqsanger.gz
	SRR11182044_2.fastq.gz	Fastqsanger.gz
	SRR11182045_1.fastq.gz	Fastqsanger.gz
	SRR11182045_2.fastq.gz	Fastqsanger.gz
	SRR11182046_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Rbfox contributes to a conservative program of self-antigen splicing in thymic epithelial cells [mTEC_bulk_RNAseq]

Project description:Rbfox contributes to a conservative program of self-antigen splicing in thymic epithelial cells [mTEC_bulk_RNAseq]

| PRJNA608750 | ENA

Rbfox contributes to a conservative program of self-antigen splicing in thymic epithelial cells [mTEC_ONT_RNAseq]

Project description:Rbfox contributes to a conservative program of self-antigen splicing in thymic epithelial cells [mTEC_ONT_RNAseq]

| PRJNA608717 | ENA

Rbfox contributes to a conservative program of self-antigen splicing in thymic epithelial cells [Rbfox_SKO_RNAseq]

Project description:Rbfox contributes to a conservative program of self-antigen splicing in thymic epithelial cells [Rbfox_SKO_RNAseq]

| PRJNA608718 | ENA

Rbfox contributes to a conservative program of self-antigen splicing in thymic epithelial cells [mTEC_bulk_RNAseq]

Project description:Thymic epithelial cells (TEC) guide selection of a T-cell repertoire that is reactive to pathogens but tolerant to self. While this process is known to involve the promiscuous expression of virtually the entire protein-coding gene repertoire by TEC, the extent to which these cells reproduce peripheral isoform structures is unknown. We performed a transcriptomic investigation of transcript structures and splicing factor expression in medullary TEC and 21 peripheral tissues. Our results indicate that TEC re-use a small number of peripheral splicing factors to recreate a limited subset of the peripheral splice isoform repertoire. We found, for example, that TEC lacked both neuronal microexons and the splicing factor, Srrm4, which promotes their inclusion. We demonstrate a functional role for the Rbfox splicing factors in promoting medullary TEC development and the alternative splicing of promiscuously expressed genes. Our findings have implications for understanding autoimmune diseases and the development of antigen-specific immunotherapies.

2021-08-03 | GSE145930 | GEO

Rbfox contributes to a conservative program of self-antigen splicing in thymic epithelial cells [mTEC_ONT_RNAseq]

2021-08-03 | GSE145914 | GEO

Rbfox contributes to a conservative program of self-antigen splicing in thymic epithelial cells [Rbfox_SKO_RNAseq]

2021-08-03 | GSE145913 | GEO

Rbfox contributes to a conservative program of self-antigen splicing in thymic epithelial cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-08-03 | GSE145931 | GEO

Splicing activation by Rbfox requires self-aggregation through its tyrosine-rich domain

Project description:To determine how the higher order assembly of Rbfox proteins affect Rbfox-dependent splicing regulation, we expressed Rbfox wildtype and its mutant protein in Flp-In™ T-REx™ 293 Rbfox2-/- cells and extracted RNA from these cells to perform RASL-seq which profiles thousands of alternative splicing event.

2017-07-13 | GSE89597 | GEO

AIRE drives early life thymic interferons and changes thymic self-antigen expression [bulk RNA-seq]

Project description:Type I interferons (IFN-I) are transiently induced during infections, but were reported to be produced in the thymus at steady state. We found that developing thymocytes displayed an IFN-I signature that was mainly dependent on IFN-β. Using Ifnb1 reporter mouse strains, we observed IFN-β expression in a small population of medullary thymic epithelial cells (mTEC), which was AIRE-dependent and peaked at 2-3 weeks of age. To study the cellular response to thymic IFN, we used a Mx1gfp reporter mouse strain and found that the IFN response in T cells and myeloid cells was abrogated by IFNaR deficiency, whereas the response in B cells and dendritic cells was dependent on both IFNaR and IFNlR. Furthermore, single-cell RNAseq analysis revealed dramatic transcriptional changes in all thymic APCs in IFNaR/IFNlR deficient mice, and a loss of CCR7+ cDC1 cells. Together, these results show that steady state IFN-I and IFN-III signaling drives a gene-expression program in thymic APCs that shapes the thymic microenvironment.

2024-09-09 | GSE192715 | GEO

Concentration-dependent regulation by Rbfox enabled by motifs of intermediate affinity

Project description:The Rbfox family of splicing factors regulate alternative splicing during animal development and in disease, impacting thousands of exons in the maturing brain, heart, and muscle. Rbfox proteins have long been known to bind to the RNA sequence GCAUG with high affinity, but just half of Rbfox CLIP peaks contain a GCAUG motif. We incubated recombinant RBFOX2 with over 60,000 mouse and human transcriptomic sequences to reveal significant binding to several moderate-affinity, non-GCAYG sites at a physiologically relevant range of RBFOX concentrations. We find that many of these “secondary motifs” bind Rbfox robustly in cells and that several together can exert regulation comparable to a GCAUG in a trichromatic splicing reporter assay. Furthermore, secondary motifs regulate RNA splicing in neuronal development and in neuronal subtypes where cellular Rbfox concentrations are highest, enabling a second wave of splicing changes as Rbfox levels increase.

2020-06-16 | GSE152510 | GEO

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