Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA319362 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We studied AES and DDX21 binding RNAs in Kasumi-1 cells stably expressing V5-tagged AES. RNA immunoprecipitation was performed with V5 antibody (for AES), DDX21 antibody and control IgG. We found that AES as well as DDX21 RIP samples showed enrichment for small nucleolar RNAs (snoRNAs) compared to control IgG. We also showed that AES and DDX21 binding snoRNAs showed significant overlap. Our studies provide mechanisms how AES regulates snoRNAs and rRNA modification.
2017-06-20 | GSE80581 | GEO
Project description:Microarray gene profilling indentified snoRNAs are downstream target of Amino Enhancer of Split (AES) and are essential for AML1-ETO9a induced leukemia. Amino Enhancer of Split (Aes) is strongly induced by leukemia oncogenes AML1-ETO, PML-RARα and PLZF-RARα. With a conditional AES knockout mouse model we showed that AES is essential for AML1-ETO9a indeced leukemia. We performed gene expression microarray using mouse primary AML1-ETO9a transformed AES wildtype and knockout and showed that snoRNAs were downregulated in AES knockout cells. We found that SnoRNA induction is a common mechanism shared by distinct oncogenes including AML1-ETO, MYC and MLL-AF9. Suppression of C/D box snoRNA complexes or deletion of several single C/D box snoRNAs inhibit clonogenic growth of leukemia cells. These findings suggest that enhancement of snoRNA levels is a critical mechanism of leukemic transformation.
2017-06-20 | GSE80579 | GEO
Project description:Leukemogenesis requires enhanced self-renewal activity, which is induced by specific oncogenes. The underlying molecular mechanisms remain incompletely understood. We transduced mouse lineage negative bone marrow cells (enriched for hematopoietic stem and progenitor cells) with retrovirus expressing leukemic oncogene AML1-ETO9a, MYC and MLL-AF9 as well as empty vector (MIG). We found that all three oncogenes enhanced snoRNA formation. High abundance of snoRNAs was observed in primary human AML specimens with the notable exception of NPM1 mutant AML. Leukemogenesis by AML1-ETO required expression of the groucho related Amino Enhancer of Split (AES). AES functioned by inducing snoRNA/RNP formation via interaction with the RNA helicase DDX21. Similarly, loss of C/D box snoRNAs with concomitant loss of rRNA 2’-O-methylation resulted in decreased leukemia self-renewal potential.In summary, we identified C/D box snoRNAs and rRNA 2’-O-methylation as critical determinants of leukemic stem cell activity.
2017-06-20 | GSE80523 | GEO
Project description:Amino Enhancer of Split (AES) is essential for AML1-ETO induced self-renewal and leukemogenesis. To study the effect of AES on transcription regulation in AML1-ETO expressing Kasumi-1 cells, nascent transcripts in control (shctr) and AES knockdown (shAES) Kasumi-1 cells were labelled with uridine analogue 4-thioduridine with subsequent nascent RNA purification and next generation sequencing (Nascent RNA-seq).
2017-06-20 | GSE80582 | GEO
Project description:DEAD-box RNA helicases are vital for the regulation of various aspects of the RNA life cycle, but the molecular underpinnings of their involvement, particularly in mammalian cells, remain poorly understood. Here we show that the DEAD-box RNA helicase DDX21 can sense transcriptional status of both RNA Pol I and Pol II to control transcriptional and post-transcriptional steps of ribosome biogenesis in human cells. We demonstrate that DDX21 widely associates with Pol I- and Pol II-transcribed genes and with diverse species of protein-coding and noncoding RNAs. Although broad, these molecular interactions, both at the chromatin and at the RNA level, exhibit a remarkable specificity for the ribosomal pathway. In the nucleolus, DDX21 occupies the transcribed rDNA locus, directly contacts both rRNA and snoRNAs and, as a functional component of the snoRNA ribonucleoprotein (snoRNP) complex, promotes modification of rRNA. In the nucleoplasm, DDX21 is incorporated into the 7SK snRNP complex, which facilitates DDX21 association with promoters of Pol II-transcribed genes encoding ribosomal proteins and snoRNAs. Promoter-bound DDX21 facilitates the release of P-TEFb from the 7SK snRNP, enhancing productive Pol II elongation. Altogether, we present a unifying mechanism for the coordinated regulation of ribosomal genes across nuclear compartments, and provide first evidence implicating a mammalian RNA helicase in RNA modification and Pol II elongation control. Examination of DDX21 chromatin association and DDX21 RNA interacting partners in HEK293 cells
2014-11-17 | E-GEOD-56802 | biostudies-arrayexpress
Project description:DEAD-box RNA helicases are vital for the regulation of various aspects of the RNA life cycle, but the molecular underpinnings of their involvement, particularly in mammalian cells, remain poorly understood. Here we show that the DEAD-box RNA helicase DDX21 can sense transcriptional status of both RNA Pol I and Pol II to control transcriptional and post-transcriptional steps of ribosome biogenesis in human cells. We demonstrate that DDX21 widely associates with Pol I- and Pol II-transcribed genes and with diverse species of protein-coding and noncoding RNAs. Although broad, these molecular interactions, both at the chromatin and at the RNA level, exhibit a remarkable specificity for the ribosomal pathway. In the nucleolus, DDX21 occupies the transcribed rDNA locus, directly contacts both rRNA and snoRNAs and, as a functional component of the snoRNA ribonucleoprotein (snoRNP) complex, promotes modification of rRNA. In the nucleoplasm, DDX21 is incorporated into the 7SK snRNP complex, which facilitates DDX21 association with promoters of Pol II-transcribed genes encoding ribosomal proteins and snoRNAs. Promoter-bound DDX21 facilitates the release of P-TEFb from the 7SK snRNP, enhancing productive Pol II elongation. Altogether, we present a unifying mechanism for the coordinated regulation of ribosomal genes across nuclear compartments, and provide first evidence implicating a mammalian RNA helicase in RNA modification and Pol II elongation control.
2014-11-17 | GSE56802 | GEO
Project description:Activation of PARP-1 by snoRNAs Controls Ribosome Biogenesis and Cell Growth via the RNA Helicase DDX21 (RIP-Seq)
| PRJNA475965 | ENA
Project description:C/EBPβ (CCAAT enhancer binding protein) is a transcription factor that plays a crucial role in survival and transformation of ALK+ anaplastic large cell lymphoma (ALCL). The aim of this study was to identify the downstream targets of C/EBPβ responsible for ALK-mediated oncogenesis. C/EBPβ was knocked down in ALK+ ALCL cell lines with a C/EBPβ-shRNA, followed by gene expression profiling (GEP). GEP analysis revealed a reproducible signature of genes that were significantly regulated by C/EBPβ. Classification into biological categories revealed overrepresentation of genes involved in the immune response, apoptosis and cell proliferation. Transcriptional regulation by C/EBPβ was found in 6 of 11 (BCL2A1, G0S2, TRIB1, S100A9, DDX21 and DDIT4) genes investigated by chromatin immunoprecipitation. We demonstrated that BCL2A1, G0S2 and DDX21 play a crucial role in survival and proliferation of ALK+ ALCL cells. DDX21, a gene involved in rRNA biogenesis, was found differentially overexpressed in primary ALK+ ALCL cases. All three candidate genes were validated in primary ALCL cases by either immunohistochemistry or RT-qPCR. In conclusion, we identified and validated several key C/EBPβ-regulated genes with major impact on survival and cell growth in ALK+ ALCL, supporting the central role of C/EBPβ in ALK-mediated oncogenesis. Kijk and SUDHL1 cell lines transfected with shRNA for C/EBPbeta were compared to control cells (3 biological replicates per group) and untreated cells (1 biological replicate)
2013-07-10 | E-GEOD-23368 | biostudies-arrayexpress
Project description:Glucose is an important cellular energy source, however, glucose’s function as a second messenger remains relatively unexplored. Here, we find that glucose binds directly to DDX21 to regulate its function during epidermal differentiation. Specifically, glucose binds to the ATP-binding domain of DDX21 to induce a conformational change and inhibit helicase activity. Glucose binding inhibits the dimerization of DDX21 leading to re-localization from the nucleolus to the nucleoplasm and reassembly of DDX21 into larger protein complexes, increasing its association with splicing factors. This occurs during keratinocyte differentiation, where glucose accumulation is necessary, and results in DDX21 binding to RNA processing proteins and mRNA introns. Consequently, DDX21 regulates the splicing of key differentiation factors and promotes epidermal differentiation in a glucose-dependent manner. These findings reveal a novel mechanism of glucose regulation of cell signaling.
2023-01-02 | GSE189910 | GEO
Project description:Glucose is an important cellular energy source, however, glucose’s function as a second messenger remains relatively unexplored. Here, we find that glucose binds directly to DDX21 to regulate its function during epidermal differentiation. Specifically, glucose binds to the ATP-binding domain of DDX21 to induce a conformational change and inhibit helicase activity. Glucose binding inhibits the dimerization of DDX21 leading to re-localization from the nucleolus to the nucleoplasm and reassembly of DDX21 into larger protein complexes, increasing its association with splicing factors. This occurs during keratinocyte differentiation, where glucose accumulation is necessary, and results in DDX21 binding to RNA processing proteins and mRNA introns. Consequently, DDX21 regulates the splicing of key differentiation factors and promotes epidermal differentiation in a glucose-dependent manner. These findings reveal a novel mechanism of glucose regulation of cell signaling.
2023-01-02 | GSE189414 | GEO