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

Cell Rep. 2018 Feb 13;22(7):1861-1874. doi: 10.1016/j.celrep.2018.01.061.

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.

Keywords: DNA repeats; RNA modification; chromatin; cytosine-5 RNA methylation; genome integrity; mobile elements; tRNA fragments; transfer RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biocatalysis
  • DNA (Cytosine-5-)-Methyltransferases / chemistry
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation / genetics
  • DNA Transposable Elements / genetics
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / enzymology*
  • Drosophila melanogaster / 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

Substances

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