<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Characterization of the Biological Function of Dnmt2\r\nin Drosophila melanogaster"^^ . "Dnmt2 genes encode highly conserved and widely distributed RNA methyltransferases with\r\npoorly understood biological functions. Recently, it has been shown that Dnmt2-mediated\r\ntRNA methylation interfered with stress-induced tRNA fragmentation, which suggested roles\r\nfor Dnmt2 during cellular stress responses.\r\nThe aim of this work was to investigate the roles of Dnmt2 during the response to\r\nbiotic (pathogens), abiotic (heat) and endogenous RNA (transposon) stress in an attempt to\r\nfurther characterize the biological function of Dnmt2. Using the model organism Drosophila\r\nmelanogaster and molecular and biochemical approaches this investigation revealed\r\nimportant roles for Dnmt2 in the control of exogenous and endogenous mobile elements.\r\nDnmt2 mutants showed stress- and age-dependent morphological phenotypes.\r\nMolecular analysis identified increased levels of RNA viruses in Dnmt2 mutants and virus\r\ninfection experiments confirmed that Dnmt2 mutants failed to control specific pathogens like\r\nDrosophila C virus (DCV). Expression analysis for immune response genes showed that\r\nDnmt2 mutant flies were not able to efficiently activate innate immune responses.\r\nImportantly, the RNA methyltransferase function of Dnmt2 contributed to virus control and\r\nbinding of Dnmt2-containing protein complexes to DCV-derived RNA implicated RNA\r\nmethylation in the process. These findings revealed a novel biological role for Dnmt2\r\nenzymes and suggest that RNA methylation may regulate viral RNA metabolism.\r\nTo extend the investigation of Dnmt2 function in mobile element control to\r\nendogenous sequences, transposon control in Dnmt2 mutants was investigated. Dnmt2\r\nmutants showed defects in the re-silencing of heat shock-induced transposons and this\r\ndepended on the catalytic activity of Dnmt2. Furthermore, increased transposon-derived\r\nDNA and transposon mobility could be detected in Dnmt2 mutants. Heat shock caused\r\nsignificantly different tRNA fragmentation patterns in Dnmt2 mutants and Dnmt2 substrate\r\ntRNA fragments associated with Argonaute-2 after heat shock. Further analysis showed that\r\nDnmt2 mutants accumulated increasing levels of Dicer-2-dependent double-stranded RNA\r\nprecursors leading to inefficient endo-siRNA production. Consequently, Dnmt2 mutants\r\ndisplayed signs of mis-regulated siRNA pathways including reduced transposon silencing,\r\nwhich led to genomic instability. These findings uncovered a stress-related function for\r\nDnmt2 in transposon regulation, which suggests that the increase in stress-induced tRNA\r\nfragments in Dnmt2 mutants affects the efficiency of small RNAi pathways.\r\nThis thesis describes novel functions of Dnmt2 in cellular stress responses to biotic\r\nand abiotic stresses and indicates that the high conservation of Dnmt2 enzymes is founded\r\nin its contribution to defense mechanisms against external and internal mobile elements."^^ . "2013" . . . . . . . "Zeljko"^^ . "Durdevic"^^ . "Zeljko Durdevic"^^ . . . . . . "Characterization of the Biological Function of Dnmt2\r\nin Drosophila melanogaster (PDF)"^^ . . . "Characterization of the Biological Function of Dnmt2 in Drosophila melanogaster.pdf"^^ . . . "Characterization of the Biological Function of Dnmt2\r\nin Drosophila melanogaster (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Characterization of the Biological Function of Dnmt2\r\nin Drosophila melanogaster (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Characterization of the Biological Function of Dnmt2\r\nin Drosophila melanogaster (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Characterization of the Biological Function of Dnmt2\r\nin Drosophila melanogaster (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Characterization of the Biological Function of Dnmt2\r\nin Drosophila melanogaster (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #15196 \n\nCharacterization of the Biological Function of Dnmt2 \nin Drosophila melanogaster\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .