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Journal ArticleDOI

Methylation of tRNAAsp by the DNA Methyltransferase Homolog Dnmt2

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TLDR
The sequence and the structure of DNA methyltransferase-2 (DnMT2) bear close affinities to authentic DNA cytosine methyltransferases, and human DNMT2 protein restored methylation in vitro to tRNAAsp from Dnmt2-deficient strains of mouse, Arabidopsis thaliana, and Drosophila melanogaster in a manner that was dependent on preexisting patterns of modified nucleosides.
Abstract
The sequence and the structure of DNA methyltransferase-2 (Dnmt2) bear close affinities to authentic DNA cytosine methyltransferases. A combined genetic and biochemical approach revealed that human DNMT2 did not methylate DNA but instead methylated a small RNA; mass spectrometry showed that this RNA is aspartic acid transfer RNA (tRNA(Asp)) and that DNMT2 specifically methylated cytosine 38 in the anticodon loop. The function of DNMT2 is highly conserved, and human DNMT2 protein restored methylation in vitro to tRNA(Asp) from Dnmt2-deficient strains of mouse, Arabidopsis thaliana, and Drosophila melanogaster in a manner that was dependent on preexisting patterns of modified nucleosides. Indirect sequence recognition is also a feature of eukaryotic DNA methyltransferases, which may have arisen from a Dnmt2-like RNA methyltransferase.

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Journal ArticleDOI

Epigenetic modifications and human disease

TL;DR: A comprehensive understanding of epigenetic mechanisms, their interactions and alterations in health and disease, has become a priority in biomedical research.
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Post-transcriptional gene regulation by mRNA modifications

TL;DR: N6-adenosine methylation directs mRNAs to distinct fates by grouping them for differential processing, translation and decay in processes such as cell differentiation, embryonic development and stress responses.
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The DNA methyltransferase family: a versatile toolkit for epigenetic regulation

TL;DR: Analysis of molecular interactions and changes in gene copy numbers modulate the activity of DNMTs in diverse gene regulatory functions, including transcriptional silencing, transcriptional activation and post-transcriptional regulation by DNMT2-dependent tRNA methylation enables the DNMT family to function as a versatile toolkit for epigenetic regulation.
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Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA

TL;DR: The widespread presence of modified cytosines throughout coding and non-coding sequences in a transcriptome is demonstrated, suggesting a broader role of this modification in the post-transcriptional control of cellular RNA function.
Journal ArticleDOI

Rethinking how DNA methylation patterns are maintained

TL;DR: A new model is proposed that suggests that the maintenance of DNA methylation relies not only on the recognition of hemimethylated DNA by DNA methyltransferase 1 (DNMT1) but also on the localization of the DNMT3A andDNMT3B enzymes to specific chromatin regions that contain methylated DNA.
References
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Journal ArticleDOI

Eukaryotic cytosine methyltransferases.

TL;DR: There are multiple families of DNA (cytosine-5) methyltransferases in eukaryotes, and each family appears to be controlled by different regulatory inputs.
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Compilation of tRNA sequences and sequences of tRNA genes

TL;DR: Alignment of the sequences, which is most compatible with the tRNA phylogeny and known three-dimensional structures of tRNA, is used.
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A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei

TL;DR: Analysis of DNA MTase-beta-galactosidase fusion proteins has shown that association with replication foci is mediated by a novel targeting sequence located near the N-terminus of DNAMTase.
Journal ArticleDOI

AdoMet-dependent methylation, DNA methyltransferases and base flipping

TL;DR: Structurally characterized AdoMet-dependent methyltransferases have been characterized structurally by X-ray crystallography and NMR and are likely to prove general for enzymes that require access to unpaired, mismatched or damaged nucleotides within base-paired regions in DNA and RNA.
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