ArticleScientific reports2017
Drosophila CG3303 is an essential endoribonuclease linked to TDP-43-mediated neurodegeneration.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Molecular basis for the calcium-dependent activation of the ribonuclease EndoU.Nature communications · 2025Article
- Article
- The endoribonuclease Arlr is required to maintain lipid homeostasis by downregulating lipolytic genes during aging.Nature communications · 2023Article
- Article
- The secreted endoribonuclease ENDU-2 from the soma protects germline immortality in C. elegans.Nature communications · 2021Article
- Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2.Protein science : a publication of the Protein Society · 2020Article
- An ancient evolutionary connection between Ribonuclease A and EndoU families.RNA (New York, N.Y.) · 2020Article
- Regulation of Nucleotide Metabolism and Germline Proliferation in Response to Nucleotide Imbalance and Genotoxic Stresses by EndoU Nuclease.Cell reports · 2020Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoribonucleases participate in almost every step of eukaryotic RNA metabolism, acting either as degradative or biosynthetic enzymes. We previously identified the founding member of the Eukaryotic EndoU ribonuclease family, whose components display unique biochemical features and are flexibly involved in important biological processes, such as ribosome biogenesis, tumorigenesis and viral replication. Here we report the discovery of the CG3303 gene product, which we named DendoU, as a novel family member in Drosophila. Functional characterisation revealed that DendoU is essential for Drosophila viability and nervous system activity. Pan-neuronal silencing of dendoU resulted in fly immature phenotypes, highly reduced lifespan and dramatic motor performance defects. Neuron-subtype selective silencing showed that DendoU is particularly important in cholinergic circuits. At the molecular level, we unveiled that DendoU is a positive regulator of the neurodegeneration-associated protein dTDP-43, whose downregulation recapitulates the ensemble of dendoU-dependent phenotypes. This interdisciplinary work, which comprehends in silico, in vitro and in vivo studies, unveils a relevant role for DendoU in Drosophila nervous system physio-pathology and highlights that DendoU-mediated neurotoxicity is, at least in part, contributed by dTDP-43 loss-of-function.
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