Immune-inducible non-coding RNA molecule lincRNA-IBIN connects immunity and metabolism in Drosophila melanogaster

Valanne, Susanna; Salminen, Tiina S.; Järvelä-Stölting, Mirva; Vesala, Laura; Rämet, Mika

doi:10.1371/journal.ppat.1007504

Cited by 49 publications

(66 citation statements)

References 86 publications

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“…This signal had not been detected previously because in the wild type it lies in the shoulder of the robust Dso1(IM4) peak. Its existence in Toll-induced hemolymph was expected, however, on the basis of microarray and RNAseq data demonstrating strong Toll-activated induction of the BomS5 locus (15,30).…”

Section: Generation Of Flies Null For the Daisho Gene Pairmentioning

confidence: 99%

The Daisho Peptides Mediate Drosophila Defense Against a Subset of Filamentous Fungi

Cohen

Lindsay

et al. 2020

Front. Immunol.

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Fungal infections, widespread throughout the world, affect a broad range of life forms, including agriculturally relevant plants, humans, and insects. In defending against fungal infections, the fruit fly Drosophila melanogaster employs the Toll pathway to induce a large number of immune peptides. Some have been investigated, such as the antimicrobial peptides (AMPs) and Bomanins (Boms); many, however, remain uncharacterized. Here, we examine the role in innate immunity of two related peptides, Daisho1 and Daisho2 (formerly IM4 and IM14, respectively), found in hemolymph following Toll pathway activation. By generating a CRISPR/Cas9 knockout of both genes, daisho, we find that the Daisho peptides are required for defense against a subset of filamentous fungi, including Fusarium oxysporum, but not other Toll-inducible pathogens, such as Enterococcus faecalis and Candida glabrata. Analysis of null alleles and transgenes revealed that the two daisho genes are each required for defense, although their functions partially overlap. Generating and assaying a genomic epitope-tagged Daisho2 construct, we detected interaction in vitro of Daisho2 peptide in hemolymph with the hyphae of F. oxysporum. Together, these results identify the Daisho peptides as a new class of innate immune effectors with humoral activity against a select set of filamentous fungi.

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Section: Generation Of Flies Null For the Daisho Gene Pairmentioning

confidence: 99%

The Daisho Peptides Mediate Drosophila Defense Against a Subset of Filamentous Fungi

Cohen

Lindsay

et al. 2020

Front. Immunol.

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“…The bombardier (bbd) gene contains a consensus Toll-responsive NF-κB binding site within its promoter region and is strongly expressed upon Toll activation by Gram-positive bacterial infection or other inducers (14,17,35,36). The encoded protein is predicted to be secreted and to generate a mature protein of 222 amino acids with a coiled coil near its C-terminus (37,38).…”

Section: The Bombardier Gene Is Specifically Required For Toll-mediatmentioning

confidence: 99%

“…This suggests a mislocalization of these peptides, perhaps in an unprocessed or misfolded state. Given that short-form Bom genes are among the most abundantly transcribed genes after infection (17,36), such mislocalized or misfolded Boms could rapidly accumulate to high levels in bbd flies. Could this explain the death of bbd flies upon immune stimulation?…”

Section: Immune Activation Specifically Bom Expression Is Deleteriomentioning

confidence: 99%

Bombardier Enables Delivery of Short-Form Bomanins in the Drosophila Toll Response

et al. 2020

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Toll mediates a robust and effective innate immune response across vertebrates and invertebrates. In Drosophila melanogaster, activation of Toll by systemic infection drives the accumulation of a rich repertoire of immune effectors in hemolymph, including the recently characterized Bomanins, as well as the classical antimicrobial peptides (AMPs). Here we report the functional characterization of a Toll-induced hemolymph protein encoded by the bombardier (CG18067) gene. Using the CRISPR/Cas9 system to generate a precise deletion of the bombardier transcriptional unit, we found that Bombardier is required for Toll-mediated defense against fungi and Grampositive bacteria. Assaying cell-free hemolymph, we found that the Bomanin-dependent candidacidal activity is also dependent on Bombardier, but is independent of the antifungal AMPs Drosomycin and Metchnikowin. Using mass spectrometry, we demonstrated that deletion of bombardier results in the specific absence of short-form Bomanins from hemolymph. In addition, flies lacking Bombardier exhibited a defect in pathogen tolerance that we trace to an aberrant condition triggered by Toll activation. These results lead us to a model in which the presence of Bombardier in wild-type flies enables the proper folding, secretion, or intermolecular associations of short-form Bomanins, and the absence of Bombardier disrupts one or more of these steps, resulting in defects in both immune resistance and tolerance.

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“…The mechanism of lncRNA-7SK in Drosophila , which is almost identical to that of its homolog in humans, may also result from the structural identity of the 7SK sequence in several regions between flies and humans [12]. LncRNAs in Drosophila have emerged as crucial regulators of organ development [13], neurological function [14,15], gonadal function [16], and stress response [17,18]. Here, we will briefly review the epigenetic, transcriptional, and post-transcriptional mechanisms of lncRNAs and then summarize their role in Drosophila with a particular emphasis on experimentally verified biological functions (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Insights into the Functions of LncRNAs in Drosophila

Tian

Yuán

et al. 2019

IJMS

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Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs longer than 200 nucleotides (nt). LncRNAs have high spatiotemporal specificity, and secondary structures have been preserved throughout evolution. They have been implicated in a range of biological processes and diseases and are emerging as key regulators of gene expression at the epigenetic, transcriptional, and post-transcriptional levels. Comparative analyses of lncRNA functions among multiple organisms have suggested that some of their mechanisms seem to be conserved. Transcriptome studies have found that some Drosophila lncRNAs have highly specific expression patterns in embryos, nerves, and gonads. In vivo studies of lncRNAs have revealed that dysregulated expression of lncRNAs in Drosophila may result in impaired embryo development, impaired neurological and gonadal functions, and poor stress resistance. In this review, we summarize the epigenetic, transcriptional, and post-transcriptional mechanisms of lncRNAs and mainly focus on recent insights into the transcriptome studies and biological functions of lncRNAs in Drosophila.

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Immune-inducible non-coding RNA molecule lincRNA-IBIN connects immunity and metabolism in Drosophila melanogaster

Cited by 49 publications

References 86 publications

The Daisho Peptides Mediate Drosophila Defense Against a Subset of Filamentous Fungi

The Daisho Peptides Mediate Drosophila Defense Against a Subset of Filamentous Fungi

Bombardier Enables Delivery of Short-Form Bomanins in the Drosophila Toll Response

Insights into the Functions of LncRNAs in Drosophila

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