Definition: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
Input: 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. Neuronsubtype 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 neurodegenerationassociated 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 DendoUmediated neurotoxicity is, at least in part, contributed by dTDP-43 loss-of-function. We previously identified and characterised the amphibian XendoU protein 1-3 . XendoU is an endoribonuclease involved in the biogenesis of small nucleolar RNAs, which participate in ribosome function 4,5 . Three-dimensional structure determination revealed that XendoU had a novel fold 3 , which led it to be defined the founding member of the Eukaryotic EndoU ribonuclease family by the Structure Classification of Proteins Database (SCOP) 6 . We later characterised another member of the same family, closely related to XendoU, namely human Placental Protein 11 (PP11) 7 , which is highly tissue-specific and represents a tumour-marker in several cancers. Proteins distantly related to XendoU family members are encoded by viruses. They represent genetic markers of nidoviruses 8 , which are responsible for human respiratory diseases, and the Nsp15 prototype is essential in the viral replication cycle 9,10 . Eukaryotic and viral endoribonucleases share a unique combination of biochemical features: Mn 2+ -dependent enzymatic activity, uridylates specificity, and release of products with 2′ , 3′ -cyclic phosphate termini 1,7 . In this study we investigated the role of XendoU homologs in Drosophila melanogaster. Sequence comparison detected the two protein products encoded by CG2145 and CG3303 genes as XendoU homologs. Deep biochemical analyses revealed that CG3303 product alone shares the aforementioned biochemical features. We named this protein, which is annotated by the major databases as serine protease, DendoU (Drosophila endoribonuclease U-specific). By exploiting the powerful reverse-genetics tools of the fruit fly model system, we investigated DendoU in vivo activity. The protein was found to be essential for Drosophila viability and crucial for neuronal activity. Depletion in the nervous system resulted in severe abnormalities such as immature phenotypes, highly reduced lifespan and impaired locomotion behaviour. These phenotypes overlap with those caused by loss-and gain-of-function of the neurodegeneration-associated protein dTDP-43, which we revealed to be regulated by DendoU.

Drosophila CG3303 is an essential endoribonuclease linked to TDP-43- mediated neurodegeneration OPEN