The Circular RNA Edis Regulates Neurodevelopment and Innate Immunity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA779053 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Circular RNAs (circRNAs) are widely expressed in eukaryotes. However, only a subset have been functionally characterized. We identify and validate a collection of circRNAs in Drosophila, and show that depletion of the brain-enriched circRNA Edis causes hyperactivation of antibacterial innate immunity both in cultured cells and in vivo. Notably, Edis depleted flies display heightened resistance to bacterial infection and enhanced pathogen clearance. Conversely, ectopic Edis expression blocks innate immunity signaling. In addition, inactivation of Edis in vivo leads to impaired locomotive activity and shortened lifespan. Remarkably, these phenotypes can be recapitulated with neuron-specific depletion of Edis, accompanied by defective neurodevelopment. Importantly, restoration of Edis expression suppresses both innate immunity and neurodevelopment phenotypes elicited by Edis depletion. We provide evidence that Edis encodes a functional protein that associates with and compromises the processing of the immune transcription factor Relish. Consistent with these observations, inactivation of Relish suppresses the innate immunity hyperactivation phenotype in the fly brain and rescues the neurodevelopment defects in Edis knockdown neurons. Thus, our study establishes the circRNA Edis as a key regulator of neurodevelopment and innate immunity.
2022-10-04 | GSE188484 | GEO
Project description:Circular RNAs (circRNAs) are widely expressed in eukaryotes. However, only a subset has been functionally characterized. We identify and validate a collection of circRNAs in Drosophila, and show that depletion of the brain-enriched circRNA Edis (circ_Ect4) causes hyperactivation of antibacterial innate immunity both in cultured cells and in vivo. Notably, Edis depleted flies display heightened resistance to bacterial infection and enhanced pathogen clearance. Conversely, ectopic Edis expression blocks innate immunity signaling. In addition, inactivation of Edis in vivo leads to impaired locomotor activity and shortened lifespan. Remarkably, these phenotypes can be recapitulated with neuron-specific depletion of Edis, accompanied by defective neurodevelopment. Furthermore, inactivation of Relish suppresses the innate immunity hyperactivation phenotype in the fly brain. Moreover, we provide evidence that Edis encodes a functional protein that associates with and compromises the processing and activation of the immune transcription factor Relish. Importantly, restoring Edis expression or ectopic expression of Edis-encoded protein suppresses both innate immunity and neurodevelopment phenotypes elicited by Edis depletion. Thus, our study establishes Edis as a key regulator of neurodevelopment and innate immunity.
| S-EPMC9612488 | biostudies-literature
Project description:The circular RNA circ_ATP8B regulates ROS production and antiviral immunity
| PRJNA1045534 | ENA
Project description:Structure and degradation of circular RNAs regulate PKR activation in innate immunity
| PRJNA507020 | ENA
Project description:<p>Healthy behavioral patterns could modulate organ functions to enhance the body’s immunity. However, whether exercise regulates antiviral innate immunity remains elusive. Here, we found that exercise promotes type-I IFN (IFN-I) production in the liver and enhances IFN-I immune activity of the body. Despite the possibility that many exercise-induced factors could regulate IFN-I production, we identified Gpld1 as a crucial molecule and the liver as the major organ to promote IFN-I production after exercise. Exercise largely loses the efficiency to induce IFN-I in Gpld1-/- mice. Further studies demonstrated that exercise-produced 3-hydroxybutanoic acid (3-HB) critically induces Gpld1 expression in the liver. Gpld1 blocks the PP2A-IRF3 interaction and therefore enhances IRF3 activation and IFN-I production, and improves the body’s antiviral ability. This study reveals that the exercise behavior improves antiviral innate immunity by linking the liver metabolism to systemic IFN-I activity, and uncovers an unknown function of liver cells in innate immunity.</p>
2024-04-24 | MTBLS7972 | MetaboLights
Project description:PTK6 regulates regeneration and repair of the intestinal epithelium. Analysis of publicly available datasets showed Ptk6 is upregulated in tuft cells upon activation of type 2 immunity. We found that disruption of Ptk6 influences gene expression involved in intestinal immune responses. Administration of succinate, which mimics infection and activates tuft cells, revealed PTK6-dependent activation of innate immune responses in male but not female mice. In contrast to wild type and Ptk6-/- female mice, Ptk6-/- male mice do not upregulate innate immunity or differentiation of secretory cell lineages following succinate treatment. Mechanistically, we found PTK6 regulates IL-25 expression and its effector functions, which are required for activation of type 2 innate immunity only in male mice. In patients with Crohn’s disease, PTK6 is upregulated in tuft cells in noninflamed regions of intestine. These data highlight roles for PTK6 in regulating sex differences in intestinal innate immunity and provide insight into the regulation of IL-25.
2024-08-01 | GSE243229 | GEO
Project description:The circular RNA circ_ATP8B regulates ROS production and antiviral immunity [circRNA-Seq]
| PRJNA1045541 | ENA
Project description:The circular RNA circ_ATP8B regulates ROS production and antiviral immunity [RNA-Seq]
| PRJNA1045542 | ENA
Project description:Circular RNAs (circRNAs) are widely expressed in eukaryotes. However, only a subset has been functionally characterized. We have identified and validated a collection of circular RNAs in Drosophila melanogaster. We show that the circular RNA circ_ATP8B is induced by viral infection and that depletion of circ_ATP8B, but not its linear sibling, compromises viral infection both in cultured cells and in vivo. In addition, our analyses reveal that circ_ATP8B is enriched in the fly gut and that gut-specific depletion of circ_ATP8B attenuates viral replication in an oral infection model. Furthermore, we find circ_ATP8B-depletion resulted in increased levels of reactive oxygen species (ROS) and enhanced expression of Duox (Dual oxidase), which produces ROS. Genetic and pharmacological manipulation of circ_ATP8B-depleted flies that reduce ROS levels rescue the viral replication defects elicited by circ_ATP8B depletion. Notably, circ_ATP8B and Duox associate with each other, and that expression of various versions of circ_ATP8B that are competent in binding Duox, but not a mutant circ_ATP8B that is incapable of binding Duox, restores physiological levels of ROS in circ_ATP8B-depleted cells. Lastly, our data show that Gaq, a subunit of G protein required for optimal Duox activity, acts downstream of circ_ATP8B to regulate Duox activity. We conclude that circ_ATP8B regulates anti-viral immunity by modulating Duox-dependent ROS production.
2024-05-15 | GSE248666 | GEO
Project description:Circular RNAs (circRNAs) are widely expressed in eukaryotes. However, only a subset has been functionally characterized. We have identified and validated a collection of circular RNAs in Drosophila melanogaster. We show that the circular RNA circ_ATP8B is induced by viral infection and that depletion of circ_ATP8B, but not its linear sibling, compromises viral infection both in cultured cells and in vivo. In addition, our analyses reveal that circ_ATP8B is enriched in the fly gut and that gut-specific depletion of circ_ATP8B attenuates viral replication in an oral infection model. Furthermore, we find circ_ATP8B-depletion resulted in increased levels of reactive oxygen species (ROS) and enhanced expression of Duox (Dual oxidase), which produces ROS. Genetic and pharmacological manipulation of circ_ATP8B-depleted flies that reduce ROS levels rescue the viral replication defects elicited by circ_ATP8B depletion. Notably, circ_ATP8B and Duox associate with each other, and that expression of various versions of circ_ATP8B that are competent in binding Duox, but not a mutant circ_ATP8B that is incapable of binding Duox, restores physiological levels of ROS in circ_ATP8B-depleted cells. Lastly, our data show that Gaq, a subunit of G protein required for optimal Duox activity, acts downstream of circ_ATP8B to regulate Duox activity. We conclude that circ_ATP8B regulates anti-viral immunity by modulating Duox-dependent ROS production.
2024-05-15 | GSE248665 | GEO