Pediastrum duplex
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA317025 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A subset of long-noncoding RNAs (lncRNAs) are spatially correlated with transcription factors (TFs) across the genome, but how these lncRNA-TF gene duplexes regulate tissue development and homeostasis is unclear. We have identified a feedback loop within the NANCI-Nkx2.1 gene duplex that is essential for buffering Nkx2.1 expression, lung epithelial cell identity, and tissue homeostasis. Within this locus, Nkx2.1 directly inhibits NANCI, while NANCI acts in cis to promote Nkx2.1 transcription. Although loss of NANCI alone does not adversely affect lung development, concurrent heterozygous mutations in both NANCI and Nkx2.1 leads to persistent Nkx2.1 deficiency and reprogramming of lung epithelial cells to a posterior endoderm fate. This disruption in the NANCI-Nkx2.1 gene duplex results in a defective perinatal innate immune response, tissue damage, and progressive degeneration of the adult lung. These data point to a mechanism where lncRNAs act as rheostats within lncRNA-TF gene duplex loci that buffer TF expression, thereby maintaining tissue specific cellular identity during development and postnatal homeostasis.
2017-09-08 | GSE92304 | GEO
Project description:Here we describe a new class of immunostimulatory short duplex RNAs that potently induce production of type I interferon (IFN-I), and particularly IFN-β, in a wide range ofhuman cell types via end-to-end dimerization, direct binding to RIG-I, and activation of the RIG-I/IRF3 pathway. These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique conserved sequence motif (sense strand: 5’-C, antisense strand: 3’-GGG) that mediates the self-assembly of end-to-end RNA dimers by Hoogsteen G-G base-pairing. The presence of terminal hydroxyl or monophosphate groups, blunt or overhanging ends, or terminal RNA or DNA bases also did not affect their ability to induce IFN-I production. Immune stimulation mediated by these duplex RNAs results in broad spectrum inhibition of infections by many respiratory viruses with pandemic potential, including SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza A, as well as the common cold virus HCoV-NL63 in cell lines and in human Lung Chips that mimic organlevel lung pathophysiology. These novel immunostimulatory motifs potentially could be harnessed to create broad-spectrum antiviral therapeutics, but they should be avoided when designing siRNAs to minimize immunological side effects.
2022-09-01 | PXD027838 | Pride
Project description:Aberrant activation of innate immune receptors can cause a spectrum of immune disorders, such as Aicardi-Goutières syndrome (AGS). One such receptor is MDA5, a viral double-stranded RNA (dsRNA) sensor that induces antiviral immune response. We here demonstrate that constitutive activation of MDA5 in AGS results from the loss of tolerance to cellular dsRNAs formed by Alu retroelements. While wild-type MDA5 cannot efficiently recognize Alu-dsRNA because its filament formation on dsRNA is impaired by the imperfect duplex structure, AGS-variants of MDA5 display reduced sensitivity to duplex structural irregularities, assembling signaling-competent filaments on Alu-dsRNA. Moreover, we identified an unexpected role of RNA-rich cellular environment in suppressing aberrant MDA5 oligomerization, highlighting context-dependence of self vs. non-self discrimination. Overall, our work demonstrates that the increased efficiency of MDA5 to recognize dsRNA comes at a cost of self-recognition, and implicates a unique role of Alu RNAs as virus-like elements that shape the primate immune system.
2018-01-29 | GSE104864 | GEO
Project description:Aberrant activation of innate immune receptors can cause a spectrum of immune disorders, such as Aicardi-Goutières syndrome (AGS). One such receptor is MDA5, a viral double-stranded RNA (dsRNA) sensor that induces antiviral immune response. We here demonstrate that constitutive activation of MDA5 in AGS results from the loss of tolerance to cellular dsRNAs formed by Alu retroelements. While wild-type MDA5 cannot efficiently recognize Alu-dsRNA because its filament formation on dsRNA is impaired by the imperfect duplex structure, AGS-variants of MDA5 display reduced sensitivity to duplex structural irregularities, assembling signaling-competent filaments on Alu-dsRNA. Moreover, we identified an unexpected role of RNA-rich cellular environment in suppressing aberrant MDA5 oligomerization, highlighting context-dependence of self vs. non-self discrimination. Overall, our work demonstrates that the increased efficiency of MDA5 to recognize dsRNA comes at a cost of self-recognition, and implicates a unique role of Alu RNAs as virus-like elements that shape the primate immune system.
2018-01-29 | GSE103539 | GEO
Project description:Here we describe a new class of immunostimulatory short duplex RNAs that potently induce production of type I interferon (IFN-I), and particularly IFN-β, in a wide range of human cell types via end-to-end dimerization, direct binding to RIG-I, and activation of the RIG-I/IRF3 pathway. These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique conserved sequence motif (sense strand: 5’-C, antisense strand: 3’-GGG) that mediates the self-assembly of end-to-end RNA dimers by Hoogsteen G-G base-pairing. The presence of terminal hydroxyl or monophosphate groups, blunt or overhanging ends, or terminal RNA or DNA bases also did not affect their ability to induce IFN-I production. Immune stimulation mediated by these duplex RNAs results in broad spectrum inhibition of infections by many respiratory viruses with pandemic potential, including SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza A, as well as the common cold virus HCoV-NL63 in cell lines and in human Lung Chips that mimic organlevel lung pathophysiology. These novel immunostimulatory motifs potentially could be harnessed to create broad-spectrum antiviral therapeutics, but they should be avoided when designing siRNAs to minimize immunological side effects.
2021-08-12 | GSE181827 | GEO
Project description:ADAR1-editing of cellular and measles virus-derived duplex RNA
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Project description:RNA duplex map in living cells reveals higher order transcriptome structure
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Project description:Breaching self-tolerance to Alu duplex RNA underlies MDA5-mediated inflammation
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Project description:Ribosome profiling is a technique that permits genome-wide, quantitative analysis of translation and has found broad application in recent years. A key step is the depletion of ribosomal RNA that allows sufficient depth of sequencing of the mRNA undergoing ribosomal translation. These data are designed to compare four strategies for ribosomal depletion; a novel strategy based on duplex-specific nuclease using either one or two cycles, the antisense oligonucleotides described in Ingola et al (2012) and the commercially available RiboZero kit (with a no treatment control).
2015-10-16 | E-MTAB-3583 | biostudies-arrayexpress
Project description:NTP4 modulates miRNA accumulation via asymmetric modification of miRNA-3p/5p duplex
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