MUC1-C REGULATES NEAT1 lncRNA EXPRESSION AND PARASPECKLE FORMATION IN CANCER STEM CELLS
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE247441 | GEO | 2024/04/08
REPOSITORIES: GEO
Similar Datasets
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.
2018-11-06 | GSE110775 | GEO
Project description:NEAT1 is one of the most studied lncRNAs, in part because its silencing in mice causes defects in mammary gland development and corpus luteum formation and protects them from skin cancer development. Moreover, depleting NEAT1 in established cancer cell lines reduces growth and sensitizes cells to DNA damaging agents. However, NEAT1 produces two isoforms and because the short isoform, NEAT1_1, completely overlaps the 5' part of the long NEAT1_2 isoform, the respective contributions of each of the isoforms to these phenotypes has remained unclear. Whereas NEAT1_1 is highly expressed in most tissues, NEAT1_2 is the central architectural component of paraspeckles, which are nuclear bodies that assemble in specific tissues and cells exposed to various forms of stress. Using dual RNA-FISH to detect both NEAT1_1 outside of paraspeckles and NEAT1_2/NEAT1 inside this nuclear body, we report herein that NEAT1_1 levels are dynamically regulated during the cell cycle and targeted for degradation by the nuclear RNA exosome. Unexpectedly, however, cancer cells engineered to lack NEAT1_1, but not NEAT1_2, do not exhibit cell cycle defects. Moreover, Neat1_1-specific knockout mice do not exhibit the phenotypes observed in Neat1-deficient mice. We propose that NEAT1 functions are mainly, if not exclusively, attributable to NEAT1_2 and, by extension, to paraspeckles.
2019-09-11 | GSE137211 | GEO
Project description:MUC1-C REGULATES NEAT1 lncRNA EXPRESSION AND PARASPECKLE FORMATION IN CANCER STEM CELLS
| PRJNA1037566 | ENA
Project description:MicroRNAs (miRNAs) play crucial roles in physiological functions and diseases such as cancer, but the regulation of their nuclear biogenesis remains poorly understood. Here, BioID on Drosha, the catalytic subunit of the microprocessor complex, revealed its proximity to SFPQ, a multifunctional RNA-binding protein (RBP) notably involved in forming the paraspeckle nuclear condensates. SFPQ depletion impacted both primary and mature miRNA expression, while other crucial paraspeckle proteins or the paraspeckle scaffolding lncRNA NEAT1 did not, indicating a unique paraspeckle-independent role. Comprehensive transcriptomic analyses showed that SFPQ loss broadly affects RNA and miRNA host gene (miRNA HG) expression, influencing both their transcription and stability. Notably, SFPQ protects specific miRNA HGs, including the oncogenic miR-17~92 polycistron, from degradation by the nuclear NEXT-exosome complex. Lastly, we show that high SFPQ is tightly linked with overexpression miR-17~92 and its mature miRNAs across a broad variety of cancers. Our findings reveal a dual role for SFPQ in the regulation of miRNA HGs transcription and stability, as well as its significance in cancers.
2024-09-04 | GSE262126 | GEO
Project description:MicroRNAs (miRNAs) play crucial roles in physiological functions and diseases such as cancer, but the regulation of their nuclear biogenesis remains poorly understood. Here, BioID on Drosha, the catalytic subunit of the microprocessor complex, revealed its proximity to SFPQ, a multifunctional RNA-binding protein (RBP) notably involved in forming the paraspeckle nuclear condensates. SFPQ depletion impacted both primary and mature miRNA expression, while other crucial paraspeckle proteins or the paraspeckle scaffolding lncRNA NEAT1 did not, indicating a unique paraspeckle-independent role. Comprehensive transcriptomic analyses showed that SFPQ loss broadly affects RNA and miRNA host gene (miRNA HG) expression, influencing both their transcription and stability. Notably, SFPQ protects specific miRNA HGs, including the oncogenic miR-17~92 polycistron, from degradation by the nuclear NEXT-exosome complex. Lastly, we show that high SFPQ is tightly linked with overexpression miR-17~92 and its mature miRNAs across a broad variety of cancers. Our findings reveal a dual role for SFPQ in the regulation of miRNA HGs transcription and stability, as well as its significance in cancers.
2024-09-04 | GSE262125 | GEO
Project description:MicroRNAs (miRNAs) play crucial roles in physiological functions and diseases such as cancer, but the regulation of their nuclear biogenesis remains poorly understood. Here, BioID on Drosha, the catalytic subunit of the microprocessor complex, revealed its proximity to SFPQ, a multifunctional RNA-binding protein (RBP) notably involved in forming the paraspeckle nuclear condensates. SFPQ depletion impacted both primary and mature miRNA expression, while other crucial paraspeckle proteins or the paraspeckle scaffolding lncRNA NEAT1 did not, indicating a unique paraspeckle-independent role. Comprehensive transcriptomic analyses showed that SFPQ loss broadly affects RNA and miRNA host gene (miRNA HG) expression, influencing both their transcription and stability. Notably, SFPQ protects specific miRNA HGs, including the oncogenic miR-17~92 polycistron, from degradation by the nuclear NEXT-exosome complex. Lastly, we show that high SFPQ is tightly linked with overexpression miR-17~92 and its mature miRNAs across a broad variety of cancers. Our findings reveal a dual role for SFPQ in the regulation of miRNA HGs transcription and stability, as well as its significance in cancers.
2024-09-04 | GSE262127 | GEO
Project description:Internal ribosome entry sites (IRESs) drive translation initiation during stress. In response to hypoxia, (lymph)angiogenic factors responsible for tissue revascularization in ischemic diseases are induced by the IRES-dependent mechanism. Here we searched for IRES trans-acting factors (ITAFs) active in early hypoxia in mouse cardiomyocytes. Using knock-down and proteomics approaches, we show a link between a stressed-induced nuclear body, the paraspeckle, and IRES-dependent translation. Our data reveal that the long non-coding RNA Neat1, an essential paraspeckle component, is a key translational regulator, active on IRESs of (lymph)angiogenic and cardioprotective factor mRNAs. In addition, paraspeckle proteins p54nrb and PSPC1 as well as nucleolin and Rps2, two p54nrb-interacting proteins identified by mass spectrometry, are ITAFs for IRES subgroups. Paraspeckle thus appears as the site of IRESome assembly in the nucleus. Polysome PCR array showed that the Neat1_2 isoform widely affects translation of mRNAs containing IRESs, involved in stress response, angiogenesis or cardioprotection.
2023-01-03 | PXD024067 | Pride
Project description:To identify human genes whose expression is controled by nuclear paraspeckle, the microarray was carried out using the RNA samples prepared from the control and NEAT1 lncRNA knockdown HeLa cells where the nucelar paraspckels were disintegrated. NEAT1 lncRNA was eliminated by administration of antisense oligogapmer. Either NEAT1 ASO (#12) or control ASO (GFP) was ademnistered into HeLa cells to knockdown NEAT1 lncRNA. Total RNAs were prepared after 6, 12 and 24 hours after ASO administration.
2013-03-15 | E-GEOD-45158 | biostudies-arrayexpress
Project description:Alternative RNA 3’-end processing provides an important source of transcriptome diversification, which impacts various biological processes and the etiology of diseases, including cancer. A prime example of this is the transcript isoform switch that leads to the read-through expression of the long non-coding RNA NEAT1_2, at the expense of the shorter polyadenylated transcript NEAT1_1. Expression of NEAT1_2 is required for the formation of paraspeckles (PS), nuclear bodies that protect cancer cells from oncogene-induced replication stress and chemotherapy. Searching for proteins that modulate this isoform switching event we identified factors involved in the 3’-end processing of polyadenylated (pA+) RNA as well as several components of the Integrator complex. Perturbation experiments established that, by promoting the cleavage of NEAT1_2, Integrator forces NEAT1_2 to NEAT1_1 isoform switching and, thereby, restrains PS assembly. Consistently, low expression levels of several Integrator subunits correlated with poorer prognosis of cancer patients exposed to chemotherapeutics. Our study identifies Integrator as a key regulator of PS biogenesis and establish a link between Integrator, cancer biology and chemosensitivity, which may be exploited therapeutically.
2020-08-21 | GSE148755 | GEO
Project description:Genome-wide screening of NEAT1 regulators reveals mito-paraspeckle communication
| PRJNA434519 | ENA