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The RNA-binding protein Arpp21 interacts with and promotes Rag1 target mRNA expression to enable TCR rearrangement [CLIP-seq]

ABSTRACT: The RNA-binding protein Arpp21 interacts with and promotes Rag1 target mRNA expression to enable TCR rearrangement [CLIP-seq]

PROVIDER: PRJNA816896 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18355503.fastq.gz	Fastqsanger.gz
	SRR18355504.fastq.gz	Fastqsanger.gz
	SRR18355505.fastq.gz	Fastqsanger.gz
	SRR18355506.fastq.gz	Fastqsanger.gz
	SRR18355507.fastq.gz	Fastqsanger.gz

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The RNA-binding protein Arpp21 interacts with and promotes Rag1 target mRNA expression to enable TCR rearrangement [CLIP-seq]

Project description:Post-transcriptional control by RNA-binding proteins (RBPs) is an essential layer of gene regulation in lymphocytes. Here, we show how members of the R3hdm RBP family regulate gene expression and promote the development of thymocytes. R3hdm paralogs with an intact R3H/SUZ domain bound mRNAs of other RBPs including Roquin-1, Roquin-2 and Nufip2, and augmented their expression. Arpp21 (R3hdm3) expression was restricted to thymocyte stages when Rag proteins recombine gene segments of the TCR variable region. Crosslinking and immunoprecipitation of Arpp21 in thymocytes revealed prominent binding to the Rag1 mRNA, and Arpp21 increased Rag1 3'-UTR reporter expression. Consequently, Arpp21–deficient mice showed decreased Rag1 expression in thymocytes, delayed TCR rearrangement, reduced frequencies of cells with TCR expression and a partial block of thymocyte development. The Arpp21 protein was regulated by Ca2+–signals that induced phosphorylation, polyubiquitination and proteasomal degradation. These findings involve general redundant functions of R3hdm RBP family proteins and show how stage-specific upregulation of Arpp21 in thymocytes promotes Rag1 expression preceding recombination while productive TCR rearrangement ceases this function.

2024-01-16 | GSE198796 | GEO

The RNA-binding protein Arpp21 interacts with and promotes Rag1 target mRNA expression to enable TCR rearrangement [RNA-seq]

2024-01-16 | GSE198797 | GEO

The RNA-binding protein Arpp21 interacts with and promotes Rag1 target mRNA expression to enable TCR rearrangement

Project description:The RNA-binding protein Arpp21 interacts with and promotes Rag1 target mRNA expression to enable TCR rearrangement

| PRJNA816895 | ENA

The RNA-binding protein Arpp21 interacts with and promotes Rag1 target mRNA expression to enable TCR rearrangement [RNA-seq]

Project description:The RNA-binding protein Arpp21 interacts with and promotes Rag1 target mRNA expression to enable TCR rearrangement [RNA-seq]

| PRJNA816898 | ENA

The thymocyte-specific RNA-binding protein Arpp21 provides TCR repertoire diversity by binding to the 3'-UTR and promoting Rag1 mRNA expression

Project description:The regulation of thymocyte development by RNA-binding proteins (RBPs) is largely unexplored. We identified 642 RBPs in the thymus and focused on Arpp21, which shows selective and dynamic expression in early thymocytes. Arpp21 was downregulated in response to T cell receptor (TCR) and Ca2+ signals. Downregulation required Stim1/Stim2 and CaMK4 expression and involved Arpp21 protein phosphorylation, polyubiquitination and proteasomal degradation. Arpp21 directly bound RNA through its R3H domain, with a preference for uridine-rich motifs, promoting the expression of target mRNAs. Analysis of the Arpp21-bound transcriptome revealed strong interactions with the Rag1 3'-UTR. Arpp21-deficient thymocytes showed reduced Rag1 expression, delayed TCR rearrangement and a less diverse TCR repertoire. This phenotype was recapitulated in Rag1 3'-UTR mutant mice harboring a deletion of the Arpp21 response region. These findings show how thymocyte-specific Arpp21 promotes Rag1 expression to enable TCR repertoire diversity until signals from the TCR terminate Arpp21 and Rag1 activities.

2023-03-31 | MSV000091606 | MassIVE

The RNA-binding protein Arpp21 interacts with and promotes Rag1 target mRNA expression to enable TCR rearrangement

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

2024-01-16 | GSE198798 | GEO

Efect of Arpp21 deficiency on TCR repertoire diversity

Project description:To assess the impact of Arpp21 deficiency on the TCR repertoire, we generated Arpp21-deficient mice from which we isolated CD4 T cells and subjected them to NGS sequencing.

2024-01-17 | GSE226369 | GEO

iCLIP of the RNA-binding protein ARPP21

Project description:About half of all human and mouse miRNA genes are located within introns of protein-coding genes. Despite this, little is known about functional interactions between miRNAs and their host genes. The intronic miRNA miR-128 regulates neuronal excitability and controls dendrite outgrowth of projection neurons during development of the mouse cerebral cortex. Its host genes R3hdm1 and Arpp21 encode highly conserved, putative RNA-binding proteins. Here we use iCLIP to describe the RNA-binding activity of ARPP21, which recognizes uridine-rich sequences with exquisite sensitivity for 3UTRs. Surprisingly, ARPP21 antagonizes miR-128 activity by co-regulating a subset of miR-128 target mRNAs enriched for neurodevelopmental functions. In contrast to miR-128, we show that ARPP21 acts as a positive post-transcriptional regulator, at least in part through interaction with the eukaryotic translation initiation complex eIF4F. This molecular antagonism is also reflected in inverse activities during dendritogenesis: miR-128 overexpression or knockdown of ARPP21 reduces dendritic complexity; ectopic ARPP21 leads to an increase. The regulatory interaction between ARPP21 and miR-128 is a unique example of convergent function by two products of a single gene.

2018-02-23 | E-MTAB-5911 | biostudies-arrayexpress

An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development

Project description:Rag1 and Rag2 gene expression in CD4+CD8+ double positive (DP) thymocytes depends on the activity of a distant anti-silencer element (ASE) that counteracts the activity of an intergenic silencer. However, the mechanistic basis for ASE activity is unknown. Here we show that the ASE physically interacts with the distant Rag1 and Rag2 gene promoters in DP thymocytes, bringing the two promoters together to form an active chromatin hub. Moreover, we show that the ASE functions as a classical enhancer that can potently activate these promoters in the absence of the silencer or other locus elements. In thymocytes lacking the chromatin organizer SATB1, we identified a partial defect in Tcra gene rearrangement that was associated with reduced expression of Rag1 and Rag2 at the DP stage. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters. Our results provide a novel framework for understanding ASE function and demonstrate a novel role for SATB1 as a regulator of Rag locus organization and gene expression in DP thymocytes. Sequencing of Satb1-ChIP and input control from 6 wk old thymus

2015-02-25 | E-GEOD-66248 | biostudies-arrayexpress

Transcriptional profiling of rag1 deficient (rag1-/-) and rag1 heterozygous (rag1+/-) zebrafish kidney and intestine

Project description:Four dual hybridizations of rag1 deficient (rag1-/-) and rag1 heterozygous (rag1+/-) zebrafish cRNAs from kidney and intestine. Keywords: Gene knockout

2009-01-05 | GSE12655 | GEO

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