Mutations in Cytosine-5 tRNA Methyltransferases Impact Mobile Element Expression and Genome Stability at Specific DNA Repeats.

Abstract

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.

• Authors: Bianca Genenncher, Zeljko Durdevic, Katharina Hanna, Daniela Zinkl, Mehrpouya Balaghy Mobin, Nevcin Senturk, Bruno Da Silva, Carine Legrand, Clément Carré, Frank Lyko, Matthias Schaefer
• Journal: Cell reports (Cell Rep) Vol. 22 Issue 7 Pg. 1861-1874 (02 13 2018) ISSN: 2211-1247 [Electronic] United States
• PMID: 29444437 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• DNA Transposable Elements
• Drosophila Proteins
• RNA, Transfer
• Mt2 protein, Drosophila
• DNA (Cytosine-5-)-Methyltransferases

Topics

• Amino Acid Sequence
• Animals
• Base Sequence
• Biocatalysis
• DNA (Cytosine-5-)-Methyltransferases (chemistry, genetics, metabolism)
• DNA Methylation (genetics)
• DNA Transposable Elements (genetics)
• Drosophila Proteins (chemistry, genetics, metabolism)
• Drosophila melanogaster (enzymology, genetics)
• Female
• Gene Expression Regulation
• Gene Silencing
• Genetic Loci
• Genomic Instability
• Heat-Shock Response (genetics)
• Interspersed Repetitive Sequences (genetics)
• Male
• RNA Stability
• RNA, Transfer (genetics)
• Transcriptome (genetics)
• Y Chromosome (genetics)