Mutations in Cytosine-5 tRNA Methyltransferases Impact Mobile Element Expression and Genome Stability at Specific DNA Repeats
Bianca Genenncher,
Zeljko Durdevic,
Katharina Hanna,
Daniela Zinkl,
Mehrpouya Balaghy Mobin,
Nevcin Senturk,
Bruno Da Silva,
Carine Legrand,
Clément Carré,
Frank Lyko,
Matthias Schaefer
Affiliations
Bianca Genenncher
Division of Cell and Developmental Biology, Center for Anatomy and Cell Biology, Medical University Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria
Zeljko Durdevic
Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany; Developmental Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Katharina Hanna
Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
Daniela Zinkl
Division of Cell and Developmental Biology, Center for Anatomy and Cell Biology, Medical University Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria
Mehrpouya Balaghy Mobin
Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany; Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
Nevcin Senturk
Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany; Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany
Bruno Da Silva
Drosophila Genetics and Epigenetics Lab, Sorbonne Universités, Université Pierre et Marie Curie (UPMC), CNRS, Institut de Biologie Paris Seine (IBPS), 9, Quai St Bernard, Boîte courrier 24, 75252 Paris Cedex 05, France
Carine Legrand
Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
Clément Carré
Drosophila Genetics and Epigenetics Lab, Sorbonne Universités, Université Pierre et Marie Curie (UPMC), CNRS, Institut de Biologie Paris Seine (IBPS), 9, Quai St Bernard, Boîte courrier 24, 75252 Paris Cedex 05, France
Frank Lyko
Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
Matthias Schaefer
Division of Cell and Developmental Biology, Center for Anatomy and Cell Biology, Medical University Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria; Corresponding author
Summary: The maintenance of eukaryotic genome stability is ensured by the interplay of transcriptional as well as post-transcriptional mechanisms that control recombination of repeat regions and the expression and mobility of transposable elements. We report here that mutations in two (cytosine-5) RNA methyltransferases, Dnmt2 and NSun2, impact the accumulation of mobile element-derived sequences and DNA repeat integrity in Drosophila. Loss of Dnmt2 function caused moderate effects under standard conditions, while heat shock exacerbated these effects. In contrast, NSun2 function affected mobile element expression and genome integrity in a heat shock-independent fashion. Reduced tRNA stability in both RCMT mutants indicated that tRNA-dependent processes affected mobile element expression and DNA repeat stability. Importantly, further experiments indicated that complex formation with RNA could also contribute to the impact of RCMT function on gene expression control. These results thus uncover a link between tRNA modification enzymes, the expression of repeat DNA, and genomic integrity.
