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Identification of transcriptional targets for Dif and Dorsal in intestinal cells of fly

ABSTRACT: The regulation of Toll signalling pathway in non-immune functions remains unclear. In this study, we found that Toll pathway regulates intestinal stem cells activity of drosophila. To further explore the potential regulation mechanism, we performed cleavage under target and tagmentation (Cut&Tag) analysis to identify candidate genes regulated by Dif and Dorsal (core transcription factors in Toll pathway) in total intestinal cells.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE279642 | GEO | 2025/09/18

REPOSITORIES: GEO

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Drosophila lncRNA-NANPI enhances Toll signaling pathway by interacting with Dif/Dorsal to facilitate transcription of antibacterial peptides

Project description:LncRNAs have important regulatory functions but their roles in Drosophila innate immunity are poorly understood. The Drosophila Toll signaling pathway responds to Gram-positive bacterial infection and is highly conserved with mammalian TLR signaling. Recent studies focused mainly on Toll signaling pathway regulation by protein-coding genes. In the present study, we found that lncRNA-CR33942 was upregulated after Micrococcus luteus infection. Gain-of-function and loss-of-function assays disclosed that lncRNA-CR33942 regulates the Toll signaling pathway and affects Drosophila survival. RNA-seq of infected CR33942-overexpressing flies was performed to explore the CR33942 mechanism. About 70% of all upregulated core enrichment genes in the Toll signaling pathway were antibacterial peptides and PGRPs transcribed by Dif/Dorsal. We also demonstrated CR33942 interactions with Dif/Dorsal and revealed that they induce antibacterial peptides. Hence, we renamed CR33942 as lncRNA-NANPI (NF-κB-associated non-coding RNA promotional immunology). The present study identified the novel Toll signaling pathway regulator NANPI, elucidated its mode of action, clarified the function of lncRNA, and expanded our understanding of the Toll signaling pathway.

2021-05-07 | GSE174007 | GEO

lncRNA-CR11538 functions as a decoy of Dif/Dorsal to negatively regulate Drosophila Toll immune responses

Project description:The maintenance of innate immune homeostasis is critical for animal survival to combat pathogens. Although many positive or negative protein factors have been identified, little is known about the long non-coding RNA that regulates the Toll pathway. Herein, we have discovered a novel lncRNA-CR11538 highly activated during the Drosophila response to gram+ bacterial infection. The transient overexpression of CR11538 inhibited the expression of antimicrobial peptides (Drosomycin and Metchnikowin) in vivo to suppress Toll signaling pathway. Remarkably, core enrichment genes based on RNAseq, subcellular localization and RIP suggest that CR11538 can interact with the transcription factor Dif/Dorsal in nucleus. ChIP-qPCR and dual luciferase report experiments show that CR11538 can sequester Dif/Dorsal away from the promoter thus suppressing the transcription of antimicrobial peptides. In summary, we discovered a novel lncRNA-CR11538 that negatively regulate the Drosophila Toll pathway. It broadens our understanding of the regulatory mechanism of Toll pathway involving lncRNA and provides insights for the research on innate immune system of insects and mammals.

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Comparative microarray analysis of psh and Dif mutant flies treated with Metarhizium anisopliae ARSEF 549

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lncRNA-CR46018 as a positive regulator controls Drosophila Toll immune response by interacting with Dif/Dorsal  

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Effect of Dorsal, Dif, and Relish mutation on Drosophila response to G- Bacteria

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Drosophila lncRNA-NANPI enhances Toll signaling pathway by interacting with Dif/Dorsal to facilitate transcription of antibacterial peptides

Project description:Drosophila lncRNA-NANPI enhances Toll signaling pathway by interacting with Dif/Dorsal to facilitate transcription of antibacterial peptides

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Transcription profiling of Drosophila mutant for transcription factors Dorsal, Dif, and Relish and their effect on immune response

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lncRNA-CR46018 as a positive regulator controls Drosophila Toll immune response by interacting with Dif/Dorsal  

Project description:lncRNA-CR46018 as a positive regulator controls Drosophila Toll immune response by interacting with Dif/Dorsal  

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lncRNA-CR11538 functions as a decoy of Dif/Dorsal to negatively regulate Drosophila Toll immune responses

Project description:lncRNA-CR11538 functions as a decoy of Dif/Dorsal to negatively regulate Drosophila Toll immune responses

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