Searching for human genes whose expression is controlled by nuclear paraspeckle
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE45158 | GEO | 2013/03/15
SECONDARY ACCESSION(S): PRJNA193170
REPOSITORIES: GEO
Similar Datasets
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:To ensure a robust immune response to pathogens without risking immunopathology, the kinetics and amplitude of inflammatory gene expression in macrophages need to be exqui- sitely well controlled. There is a growing appreciation for stress-responsive membraneless organelles (MLOs) regulating various steps of eukaryotic gene expression in response to extrinsic cues. Here, we implicate the nuclear paraspeckle, a highly ordered biomolecular condensate that nucleates on the Neat1 lncRNA, in tuning innate immune gene expression in murine macrophages. In response to a variety of innate agonists, macrophage paraspeckles rapidly aggregate (0.5 h poststimulation) and disaggregate (2 h poststimulation). Paraspeckle maintenance and aggregation require active transcription and MAPK signaling, whereas paraspeckle disaggregation requires degradation of Neat1 via the nuclear RNA exosome. In response to lipopolysaccharide treatment, Neat1 KO macrophages fail to properly express a large cohort of proinflammatory cytokines, chemokines, and antimicrobial mediators. Consequently, Neat1 KO macrophages cannot control replication of Salmonella enterica serovar Typhimurium or vesicular stomatitis virus. These findings highlight a prominent role for MLOs in orchestrating the macrophage response to pathogens and support a model whereby dynamic assembly and disassembly of paraspeckles reorganizes the nuclear landscape to enable inflammatory gene expression following innate stimuli.
2024-02-09 | GSE255322 | 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: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: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: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:MUC1-C subunit plays an essential role in regulating NEAT1 expression. MUC1-C activates the NEAT1 gene with induction of the NEAT1_1 and NEAT1_2 isoforms by NF-kB- and MYC-mediated mechanisms. MUC1-C/MYC signaling also induces expression of the SFPQ, NONO and FUS RNA binding proteins (RBPs) that associate with NEAT1_2 and are necessary for paraspeckle formation.
2024-04-08 | GSE247441 | GEO
Project description:Type 2 Diabetes (T2D) is a global health issue characterized by abnormal blood glucose levels and often associated with excessive hepatic gluconeogenesis. Increased circulating non-essential amino acids (NEAAs) are consistently observed in T2D individuals; however, the specific contribution of each amino acid to T2D pathogenesis remains less understood. Here, we reported an unexpected role of the NEAA proline in coordinating hepatic glucose metabolism by modulating paraspeckle, a nuclear structure scaffolded by the long noncoding RNA Neat1. Mechanistically, proline diminished paraspeckles in hepatocytes, liberating the retained mRNA species into cytoplasm for translation, including the mRNAs of Ppargc1a and Foxo1, contributing to enhanced gluconeogenesis and hyperglycemia. We further demonstrated that the proline-paraspeckle-mRNA retention axis existed in diabetic liver samples, and intervening this axis via paraspeckle restoration significantly alleviated hyperglycemia in both female and male diabetic mouse models. Collectively, our results not only delineated a previously unappreciated proline-instigated, paraspeckle-dependent mRNA retention mechanism regulating gluconeogenesis, but also spotlighted proline and paraspeckle as potential targets for managing hyperglycemia. This SuperSeries is composed of the SubSeries listed below.
2024-11-26 | GSE252452 | GEO
Project description:Type 2 Diabetes (T2D) is a global health issue characterized by abnormal blood glucose levels and often associated with excessive hepatic gluconeogenesis. Increased circulating non-essential amino acids (NEAAs) are consistently observed in T2D individuals; however, the specific contribution of each amino acid to T2D pathogenesis remains less understood. Here, we reported an unexpected role of the NEAA proline in coordinating hepatic glucose metabolism by modulating paraspeckle, a nuclear structure scaffolded by the long noncoding RNA Neat1. Mechanistically, proline diminished paraspeckles in hepatocytes, liberating the retained mRNA species into cytoplasm for translation, including the mRNAs of Ppargc1a and Foxo1, contributing to enhanced gluconeogenesis and hyperglycemia. We further demonstrated that the proline-paraspeckle-mRNA retention axis existed in diabetic liver samples, and intervening this axis via paraspeckle restoration significantly alleviated hyperglycemia in both female and male diabetic mouse models. Collectively, our results not only delineated a previously unappreciated proline-instigated, paraspeckle-dependent mRNA retention mechanism regulating gluconeogenesis, but also spotlighted proline and paraspeckle as potential targets for managing hyperglycemia.
2024-11-26 | GSE252451 | GEO