Transcriptional changes induced by changes in the SUZ-domain containing proteins SZRD1 or ARPP21
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PROVIDER: PRJEB40520 | ENA |
REPOSITORIES: ENA
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Project description:The goal of this study was to investigate transcriptional changes induced by changes in the abundance of the proteins SZRD1 or ARPP21. Both proteins contain a conserved SUZ domain and preliminary data indicated that they might interfere with the function of nonsense-mediated decay. The samples of this dataset were obtained by overexpression of either SZRD1 or ARPP21 in HeLa cells. In parallel, we knocked down SZRD1.
2023-02-27 | E-MTAB-9627 | biostudies-arrayexpress
Project description:Histone Demethylation by a Family of UBA Domain-containing Proteins
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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 | GSE198797 | GEO
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
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
Project description:Histone methyl groups can be removed by histone demethylases. Although LSD1 and JmjC domain-containing proteins have been identified to be histone demethylases, enzymes responsible for many histone methylation states or sites are not identified. Here, we performed a high-content cell-based screening of a cDNA library containing 2,500 nuclear proteins and identified KDM10A as a histone demethylase specific for histone H4 lysine 20 (H4K20). Ectopic expression of KDM10A reduced the global levels of H4K20me1/2/3 in 293T cells. In vitro, KDM10A specifically demethylated H4K20me1/2/3 and generated formaldehyde. The enzymatic activity required Fe(II) and α-ketoglutarate as cofactors. Domain mapping indicated that the demethylase activity required its UBA domain. We also demonstrated that KDM10B, a protein homologous to KDM10A, had H4K20 demethylase activity in vitro and in vivo. ChIP-seq reveals that KDM10A/B demethylated H4K20 methylation at specific genomic loci in vivo. We further demonstrated that KDM10A/B activated the transcription of coding genes by demethylating H4K20me1 in the gene body, and the transcription of repetitive elements by demethylating H4K20me3 in intergenic regions. NMR analyses demonstrated that an HxxxE motif in the UBA domain is crucial for iron binding, mutation of these two residues abolished iron binding and the demethylase activity. Thus, we identified a family of UBA domain-containing proteins as histone demethylases.
2020-03-29 | GSE135986 | GEO
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
Project description:PIWI proteins and their bound piRNAs form the core of a gonad specific small RNA silencing pathway in animals that protects the genome against the deleterious activity of transposable elements. Recent studies linked the piRNA pathway to TUDOR biology, where TUDOR domains of various proteins recognize and bind symmetrically methylated Arginine residues in PIWI proteins. We systematically analyzed the Drosophila TUDOR protein family and identified three previously not characterized TUDOR domain-containing genes (CG4771, CG14303 and CG11133) as essential piRNA pathway members. We characterized CG4771 (Avocado) in detail and demonstrate a critical role for this protein during primary piRNA biogenesis in somatic and germline cells of the ovary. Avocado physically and/or genetically interacts with the primary pathway components Piwi, Armitage, Yb and Zucchini. Avocado also interacts with the Tdrd12 orthologs CG11133 and CG31755, which are essential for primary piRNA biogenesis in the germline and probably functionally replace the related and soma specific factor Yb. small RNA libraries were prepared from total RNA isolation of 8 different genotypes
2011-08-16 | E-GEOD-30955 | biostudies-arrayexpress
Project description:PIWI proteins and their bound piRNAs form the core of a gonad specific small RNA silencing pathway in animals that protects the genome against the deleterious activity of transposable elements. Recent studies linked the piRNA pathway to TUDOR biology, where TUDOR domains of various proteins recognize and bind symmetrically methylated Arginine residues in PIWI proteins. We systematically analyzed the Drosophila TUDOR protein family and identified three previously not characterized TUDOR domain-containing genes (CG4771, CG14303 and CG11133) as essential piRNA pathway members. We characterized CG4771 (Avocado) in detail and demonstrate a critical role for this protein during primary piRNA biogenesis in somatic and germline cells of the ovary. Avocado physically and/or genetically interacts with the primary pathway components Piwi, Armitage, Yb and Zucchini. Avocado also interacts with the Tdrd12 orthologs CG11133 and CG31755, which are essential for primary piRNA biogenesis in the germline and probably functionally replace the related and soma specific factor Yb.
2011-08-16 | GSE30955 | GEO
Project description:To systematically investigate the regulations and functions of human WW-domain containing proteins, we conducted a proteomic analysis of 26 full-length WW-domain containing proteins and 17 WW-domains only, and identified their associated protein complexes in human HEK293T cells using tandem affinity purifications followed by LC-MSMS.
2019-12-02 | PXD004649 | Pride