Oncogenic properties of NEAT1 in prostate cancer cells depend on the CDC5L-AGRN transcriptional regulation circuit
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ABSTRACT:
PROVIDER: PRJNA473338 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7224920.fastq.gz | Fastqsanger.gz | |||
| SRR7224920_1.fastq.gz | Fastqsanger.gz | |||
| SRR7224920_2.fastq.gz | Fastqsanger.gz | |||
| SRR7224921_1.fastq.gz | Fastqsanger.gz | |||
| SRR7224921_2.fastq.gz | Fastqsanger.gz |
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Project description:Silencing NEAT1 in prostate cancer cells repressed the transcriptional activity of CDC5L, and RNA-seq and further analyses revealed a handful of potential targets of CDC5L regulated by NEAT1 expression. We have established the requirement of the CDC5L-AGRN circuit for the essential oncogenic role of NEAT1 in prostate cancer cells. Here we provide processed raw counts files.
2018-06-01 | GSE114959 | GEO
Project description:Although thousands of long non-coding RNAs (lncRNAs) are localized in the nucleus, only a few dozen have been functionally characterized. We found that nuclear paraspeckle assembly transcript 1 (NEAT1), an essential lncRNA for the formation of nuclear body paraspeckles, is induced by poly I:C stimulation, resulting in excess formation of paraspeckles. Using microarray analysis, we investigated whether NEAT1 induction followed by excess formation of paraspeckles was involved in poly I:C-inducible gene expression. We want to know the NEAT1-regulated genes. To the end, HeLa TO cells with and without poly I:C stimulation and NEAT1-knock down cells with and without poly I:C stimulation and cells transfected with mock plasmid or Neat1v2 expression plasmid alone were used for RNA extraction and hybridization on Affymetrix microarrays.
2014-05-07 | E-GEOD-56936 | biostudies-arrayexpress
Project description:We investigated the role of NEAT1 knockdown on neuronal excitability in iPSC-derived neurons.
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Project description:Long noncoding RNAs (lncRNAs) are important regulators of chromatin; however, the mechanistic roles for many lncRNAs are poorly understood in part because their direct interactions with genomic loci and proteins are difficult to assess. We used CHART-seq to map the genomic binding sites for two highly expressed human lncRNAs, NEAT1 and MALAT1, which localize within the nucleus to paraspeckles and nuclear speckles, respectively. We show that NEAT1 and MALAT1 localize to hundreds of genomic sites in human cells, primarily over active genes. NEAT1 and MALAT1 exhibit colocalization to many of these loci, but display distinct gene body binding patterns at these sites, suggesting independent but complementary functions for these RNAs. Protein mass spectrometry analysis of CHART-enriched material (CHART-MS) identified numerous proteins enriched by both lncRNAs, supporting complementary binding and function, in addition to unique associated proteins. Transcriptional inhibition or stimulation affects the localization of NEAT1 to active chromatin sites, implying that DNA sequence itself does not target NEAT1 to chromatin and that localization responds to cues involved in the transcription process. Paired-end CHART-seq was performed for a single replicate of each capture oligonucleotide in untreated MCF-7 cells to establish binding sites of these RNAs, for a total of 6 samples. To investigate the effects of transcriptional inhibition and E2 stimulation on the localization of these RNAs, we performed paired-end CHART-seq with each capture oligonucleotide for two biological replicates of flavopiridol- and vehicle (DMSO)-treated MCF-7 cells and for two biological replicates of E2- and vehicle (ethanol)-treated MCF-7 cells. To establish the overlap of NEAT1 and MALAT1 binding sites with a known component of paraspeckles (NEAT1-containing subnuclear body), we performed paired-end ChIP-seq for the paraspeckle component PSF in MCF-7 cells, as well as a single-end biological replicate.
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Project description:Mice lacking Astn2 have ASD-like behaviors and altered cerebellar circuit properties
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Project description:Long non-coding (lnc)RNA emerge as regulators of genome stability. The nuclear enriched abundant transcript 1 (NEAT1) is overexpressed in many tumours and responsive to genotoxic stress. However, the mechanism that links NEAT1 to DNA damage response (DDR) is unclear. Here, we investigate the expression, modification levels, localization and structure of NEAT1 in response to DNA double-strand breaks (DSBs). DNA damage increases the levels and N6-methyladenosine (m6A) marks on NEAT1, which promotes alterations in NEAT1 structure, accumulation of hyper-methylated NEAT1 at promoter-associated DSBs and DSB foci formation. The depletion of NEAT1 delays DSB signalling and elevates DNA damage. The genome-protective role of NEAT1 is mediated by the RNA methyltransferase 3 (METTL3) and involves the release of the chromodomain helicase DNA binding protein 4 (CHD4) from NEAT1 to fine-tune histone deacetylation, which links NEAT1 to DDR.
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Project description:Astrotactin 2 (ASTN2) is a transmembrane neuronal protein highly expressed in the cerebellum that functions in receptor trafficking and modulates cerebellar Purkinje cell (PC) synaptic activity. Individuals with ASTN2 mutations exhibit neurodevelopmental disorders, including autism spectrum disorder (ASD), ADHD, learning difficulties and language delay. To provide a genetic model for the role of the cerebellum in ASD-related behaviors and study the role of ASTN2 in cerebellar circuit function, we generated global and PC-specific conditional Astn2 knockout (KO and cKO, respectively) mouse lines. Astn2 KO mice exhibited strong ASD-related behavioral phenotypes, including a marked decrease in separation-induced pup ultrasonic vocalization calls, hyperactivity, and repetitive behaviors, altered behavior in the three-chamber test, and impaired cerebellar-dependent eyeblink conditioning. Hyperactivity and repetitive behaviors were also prominent in Astn2 cKO animals but they did not show altered behavior in the three-chamber test. By Golgi staining, Astn2 KO PCs had region-specific changes in dendritic spine density and filopodia numbers. Proteomic analysis of Astn2 KO cerebellum revealed a marked upregulation of ASTN2 family member, ASTN1, a neuron-glial adhesion protein. Immunohistochemistry and electron microscopy demonstrated a significant increase in Bergmann glia volume in the molecular layer of Astn2 KO animals. Electrophysiological experiments indicated a reduced frequency of spontaneous excitatory postsynaptic currents (EPSCs), as well as increased amplitudes of both spontaneous EPSCs and inhibitory postsynaptic currents (IPSCs) in the Astn2 KO animals, suggesting that pre- and postsynaptic components of synaptic transmission were altered. Thus, ASTN2 regulates ASD-like behaviors and cerebellar circuit properties.
2024-07-30 | PXD052868 | Pride
Project description:p53 is a transcriptional activator that induces myriad target genes. However, those p53-inducible genes most critical for tumor suppression remain elusive. Here, we identify Neat1, a ncRNA constituent of paraspeckles, as a p53 target gene induced by mouse and human p53 in different cell types and by diverse stress signals. Using fibroblasts derived from Neat1-/- mice, we examine the functional role of Neat1 in the p53 pathway. We find that Neat1 is dispensable for cell-cycle arrest and apoptosis in response to genotoxic stress, but plays a crucial role in suppressing transformation in response to oncogenic signals. To determine the effects of Neat1 deficiency on cells, we used E1A;HRasV12-expressing wild-type and Neat1-/- mouse embryonic fibroblasts (MEFs) for RNA-sequencing analysis. This analysis revealed that Neat1 deficiency impacts the regulatory networks involved in nervous system development and axon guidance programs, as well as genes of the SWI/SNF complex and components of the pancreas development network. These findings suggest that the ability of Neat1 to globally regulate gene expression, with effects on diverse transcriptional programs, provides a potential mechanism for how Neat1 acts to suppress transformation and tumor initiation.
2017-07-27 | GSE100098 | GEO
Project description:Long non-coding (lnc)RNA emerge as regulators of genome stability. The nuclear enriched abundant transcript 1 (NEAT1) locus encodes two lncRNA isoforms that modulate gene expression, growth and proliferation in mammals. Interestingly, NEAT1 transcripts are overexpressed in many tumours and induced by DNA damage, suggesting a genome-protective function. However, the precise role of NEAT1 in the DNA damage response (DDR) is unclear. Here, we investigate the expression, modification levels, localization and structure of NEAT1 in response to DNA double-strand breaks (DSBs) induced by the topoisomerase-II inhibitor etoposide or the locus-specific endonuclease AsiSI. We find that induction of DSBs increases both the levels and N6-methyladenosine (m6A) marks on NEAT1, which promotes alterations in NEAT1 secondary structure and accumulation of hyper-methylated NEAT1 at a subset of promoter-associated DSBs to facilitate efficient DSB signalling. The depletion of NEAT1, in turn, delays the response to DSBs and triggers elevated DNA damage. The genome-protective role of NEAT1 is mediated by the RNA methyltransferase 3 (METTL3) and involves spreading of the chromodomain helicase DNA binding protein 4 (CHD4) upon release from NEAT1. Together, we describe a novel RNA-dependent DDR pathway that couples NEAT1 to the recognition and repair of DSBs.
2024-09-17 | GSE256233 | GEO
Project description:The long non-coding RNA NEAT1 (nuclear enriched abundant transcript 1) nucleates the formation of paraspeckles, which constitute a type of nuclear body that has multiple roles in gene expression. How the NEAT1 gene itself is regulated and how paraspeckles communicate with other cell compartments remains poorly understood. Here we identify regulators of NEAT1 transcription using an endogenous NEAT1 promoter-driven EGFP reporter in human cells coupled with genome-wide RNAi screens. In addition to transcription factors and chromatin modulators, the screens unexpectedly yielded gene candidates involved in mitochondrial functions as essential regulators of NEAT1 expression and paraspeckle formation. Mitochondrial defects altered NEAT1 transcription via ATF2 and subsequently uncoupled 3’ end processing of NEAT1_1 from its long isoform to favour NEAT1_2 production, which is key for generating elongated paraspeckles that have different features from the regular, globular bodies. Correspondingly, NEAT1 depletion has profound effects on mitochondrial dynamics and function by altering sequestration of mRNAs of mitochondrial genes enriched in paraspeckles. Overall, our data provided a rich resource for understanding NEAT1 and paraspeckle regulation, and revealed an unexpected crosstalk between cytoplasmic organelles and nuclear bodies.
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