TENT5C Bcells
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB33089 | ENA |
REPOSITORIES: ENA
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Project description:B cell humoral response and differentiation is regulated by non-canonical poly(A) polymerase TENT5C.
| PRJNA549395 | ENA
Project description:FAM46C is one of the most frequently mutated genes in multiple myeloma (MM) and encodes a protein of unknown function. Using a combination of in vitro and in vivo approaches, we demonstrate that FAM46C encodes an active cytoplasmic non-canonical poly(A) polymerase, which enhances mRNA stability and gene expression. Moreover, we also found that the reintroduction of active FAM46C into MM cell lines, but not its catalytically-inactive mutant, leads to broad polyadenylation and stabilization of mRNAs strongly enriched with those encoding endoplasmic reticulum-targeted proteins and induced cell death. This is, to our knowledge, the first report that directly associates cytoplasmic poly(A) polymerase with carcinogenesis. Furthermore, our data suggest that the human genome encodes at least eleven non-canonical poly(A) polymerases with four FAM46 family members. Since FAM46 proteins are differentially expressed during development, these proteins may positively regulate transcript stability and translational rate in a tissue-specific manner.
2017-06-30 | GSE83772 | GEO
Project description:EZH2 mediates the humoral immune response and drives lymphomagenesis through de novo formation of bivalent chromatin domains and critical germinal center (GC) B cell promoters. We show that such formation is dependent on the presense of BCL6 and the presence of non-canonical PRC1-BCOR complex. We observe that BCL6 and EZH2 cooperate to accelerate diffuse large B cell lymphoma (DLBCL) development and combinatorial targeting of these repressors results in enhanced anti-lymphoma activity in vitro, in vivo, and in primary human DLBCLs. DLBCL cell lines treated with BCL6 inhibitor 79-6.1085
2016-07-20 | E-GEOD-73109 | biostudies-arrayexpress
Project description:<p>We use next generation sequencing to investigate the different transcriptomes of closely related CD4+ T-cells from healthy human donors to elucidate the genetic programs that underlie their specialized immune functions. Six cell types were included: Regulatory T-cells (CD25hiCD127low/neg with >95% FOXP3+ purity), regulatory T-cells activated using PMA/ionomycin, CD25-CD45RA+ ('naive' helper T-cells), CD25-CD45RO+ ('memory' helper T-cells), activated Th17 cells (>98% IL17A+ purity) and activated IL17-CD4+ T-cells (called 'ThPI'). Poly-T capture beads were used to isolate mRNA from total RNA, and fragment sizes of ~200 were sequenced from both ends on Illumina's genome analyzer. We confirm many of the canonical signature genes of T-cell populations, but also discover new genes whose expression is limited to specific CD4 T-cell lineages, including long non-coding RNAs. Additionally, we find that genes encoded at loci linked to multiple human autoimmune diseases are enriched for preferential expression upon T-cell activation, suggesting that an aberrant response to T-cell activation is fundamental to pathogenesis.</p>
| phs000626 | dbGaP
Project description:TENT5 cytoplasmic non-canonical poly(A) polymerases regulate the innate immune response in animals
| PRJEB40892 | ENA
Project description:Animal germline development and fertility relies on paralogs of general transcription factors that recruit RNA polymerase II to ensure cell type-specific gene expression. It remains unclear whether gene expression processes downstream of such paralog-based transcription is distinct from that of canonical RNA polymerase II genes. In Drosophila, the testis-specific TBP-associated factors (tTAFs) activate over a thousand spermatocyte-specific gene promoters to enable meiosis and germ cell differentiation. Here we show that efficient termination of tTAF-activated transcription requires a testis-specific Polymerase Associated Factor 1 Complex (tPAF) composed of paralogs of canonical Polymerase Associated Factor 1 Complex (PAF1C) proteins. Defective transcription termination in tPAF mutants causes aberrant expression of hundreds of downstream genes due to read-in transcription, compromising cell type-specific gene expression in spermatocytes. Consistently, tPAF is required for the segregation of meiotic chromosomes, sperm individualisation, and male fertility. Comparative in vivo proximity labeling assays of tPAF and PAF1C showed tPAF-specific association with tTAF as well as connections to central RNA polymerase II termination factors. Our study uncovers transcription termination as a developmentally regulated process required for cell type-specific gene expression.
2024-04-13 | PXD049360 | Pride
Project description:Animal germline development and fertility relies on paralogs of general transcription factors that recruit RNA polymerase II to ensure cell type-specific gene expression. It remains unclear whether gene expression processes downstream of such paralog-based transcription is distinct from that of canonical RNA polymerase II genes. In Drosophila, the testis-specific TBP-associated factors (tTAFs) activate over a thousand spermatocyte-specific gene promoters to enable meiosis and germ cell differentiation. Here we show that efficient termination of tTAF-activated transcription requires a testis-specific Polymerase Associated Factor 1 Complex (tPAF) composed of paralogs of canonical Polymerase Associated Factor 1 Complex (PAF1C) proteins. Defective transcription termination in tPAF mutants causes aberrant expression of hundreds of downstream genes due to read-in transcription, compromising cell type-specific gene expression in spermatocytes. Consistently, tPAF is required for the segregation of meiotic chromosomes, sperm individualisation, and male fertility. Comparative in vivo proximity labeling assays of tPAF and PAF1C showed tPAF-specific association with tTAF as well as connections to central RNA polymerase II termination factors. Our study uncovers transcription termination as a developmentally regulated process required for cell type-specific gene expression.
2024-04-13 | PXD049375 | Pride
Project description:Polyadenylation of nascent RNA by poly(A) polymerase (PAP) is important for 3’ end maturation of almost all eukaryotic mRNAs. Most mammalian genes harbor multiple polyadenylation sites (PASs), leading to expression of alternative polyadenylation (APA) isoforms with distinct functions. How poly(A) polymerases may regulate PAS usage and hence gene expression is poorly understood. Here we show that the nuclear canonical (PAPalpha and PAPgamma) and non-canonical (Star-PAP) PAPs play diverse roles in PAS selection and gene expression. Deficiencies in the PAPs resulted in perturbations of gene expression, with Star-PAP impacting lowly expressed mRNAs and long-noncoding RNAs to the greatest extent. Importantly, different PASs of a gene are distinctly regulated by different PAPs, leading to widespread relative expression changes of APA isoforms. The location and surrounding sequence motifs of a PAS appear to differentiate its regulation by the PAPs. We show Star-PAP-specific PAS usage regulates the expression of the eukaryotic translation initiation factor EIF4A1, the tumor suppressor gene PTEN, and the long non-coding RNA NEAT1. The Star-PAP-mediated APA of PTEN is essential for DNA damage-induced increase of PTEN protein levels. Together, our results reveal a PAS-guided and PAP-mediated paradigm for gene expression in response to cellular signaling cues.
2017-06-19 | GSE84461 | GEO
Project description:Mammalian genomes are pervasively transcribed outside mapped protein-coding genes. One class of extragenic transcription products is represented by long non-coding RNAs (lncRNAs), some of which result from Pol_II transcription of bona-fide RNA genes. Whether all lncRNAs described insofar are products of RNA genes, however, is still unclear. Here we have characterized transcription sites located outside protein-coding genes in a highly regulated response, macrophage activation by endotoxin. Using chromatin signatures, we could unambiguously classify extragenic Pol_II transcription sites as belonging to either canonical RNA genes or transcribed enhancers. Unexpectedly, 70% of extragenic Pol_II peaks were associated with genomic regions with a canonical chromatin signature of enhancers. Enhancer-associated extragenic transcription was frequently adjacent to inducible inflammatory genes, was regulated in response to endotoxin stimulation and generated very low abundance transcripts. Moreover, transcribed enhancers were under purifying selection and contained binding sites for inflammatory transcription factors, thus suggesting their functionality. These data demonstrate that a large fraction of extragenic Pol_II transcription sites can be ascribed to cis-regulatory genomic regions rather than to autonomous RNA genes. Discrimination between lncRNAs generated by canonical RNA genes and products of transcribed enhancers will provide a framework for experimental approaches to lncRNAs and help complete the annotation of mammalian genomes. Chromatin immunoprecipitation of RNA polymerase II phosphorylated in ser5 followed by multiparallel sequencing was performed in bone marrow-derived macrophages. The experiment was also carried out in cells treated for 2hrs with lipopolysaccharide (LPS).
2010-05-21 | E-GEOD-19991 | biostudies-arrayexpress
Project description:The Musashi family of mRNA translational regulators control both physiological and pathological stem cell self-renewal primarily by repressing targets that promote differentiation. In response to differentiation cues, Musashi can switch from a repressor to an activator of target mRNA translation. However, the molecular events that distinguish Musashi-mediated translational activation from repression are not understood. We have previously reported that Musashi function is required for the maturation of Xenopus oocytes, and specifically for translational activation of specific dormant maternal mRNAs. Here, we employed mass spectrometry to identify cellular factors necessary for Musashi-dependent mRNA translational activation. We report a requirement for association of Musashi1 with the embryonic poly(A) binding protein (ePABP) or the canonical somatic cell poly(A) binding protein PABPC1 for activation of Musashi target mRNA translation. Co-immunoprecipitation studies demonstrated an increased Musashi1 interaction with ePABP during oocyte maturation. Attenuation of endogenous ePABP activity severely compromised Musashi function, preventing downstream signaling and blocking oocyte maturation. Recovery of Musashi-dependent mRNA translational activation and maturation of ePABP attenuated oocytes was achieved through ectopic expression of either ePABP or PABPC1. Consistent with the findings in Xenopus oocytes, PABPC1 remained associated with Musashi under conditions of Musashi target mRNA de-repression and translation during mammalian stem cell differentiation. Since association of Musashi1 with poly(A) binding proteins has previously only been implicated in repression of Musashi target mRNAs, our findings reveal distinct context-dependent roles for the interaction of Musashi with poly[A] binding protein family members in response to extracellular cues that control cell fate.
2019-05-31 | PXD013585 | Pride