Methylation of tRNA
            <sup>Asp</sup>
            by the DNA Methyltransferase Homolog Dnmt2

Goll, Mary; Kirpekar, Finn; Maggert, Keith A.; Yoder, Jeffrey A.; Hsieh, Chih Lin; Zhang, Xiaoyu; Golic, Kent G.; Jacobsen, Steven E.; Bestor, Timothy H.

doi:10.1126/science.1120976

Cited by 1,002 publications

(872 citation statements)

References 21 publications

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“…While a similar shift to RNA specificity has been reported among eukaryotic C5‐MTases, i.e. DNMT2 39, 89 and at least in one clade of TET/JBP enzymes 15, 90, it appears to be more common in N 6 A‐MTases. This difference might be related to the distinct C‐terminal module in C5‐MTases that predisposes them to preferentially bind dsDNA 20.…”

Section: Evolutionary Trends In Eukaryotic N6a‐mtasessupporting

confidence: 67%

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

2015

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While N6‐methyladenosine (m6A) is a well‐known epigenetic modification in bacterial DNA, it remained largely unstudied in eukaryotes. Recent studies have brought to fore its potential epigenetic role across diverse eukaryotes with biological consequences, which are distinct and possibly even opposite to the well‐studied 5‐methylcytosine mark. Adenine methyltransferases appear to have been independently acquired by eukaryotes on at least 13 occasions from prokaryotic restriction‐modification and counter‐restriction systems. On at least four to five instances, these methyltransferases were recruited as RNA methylases. Thus, m6A marks in eukaryotic DNA and RNA might be more widespread and diversified than previously believed. Several m6A‐binding protein domains from prokaryotes were also acquired by eukaryotes, facilitating prediction of potential readers for these marks. Further, multiple lineages of the AlkB family of dioxygenases have been recruited as m6A demethylases. Although members of the TET/JBP family of dioxygenases have also been suggested to be m6A demethylases, this proposal needs more careful evaluation.Also watch the Video Abstract.

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Section: Evolutionary Trends In Eukaryotic N6a‐mtasessupporting

confidence: 67%

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

2015

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“…m 5 C modifications can be installed by any of the seven proteins of the Nol1/Nop2/SUN domain (NSUN) family and by an enzyme named DNA methyltransferase 2 (DNMT2). DNMT2 mainly catalyses the m 5 C modification in position 38 of tRNA Asp in human cells (Goll et al , 2006), while the so far characterised NSUN proteins show specificity for tRNAs (NSUN2, NSUN6; Schaefer et al , 2010; Tuorto et al , 2012; Blanco et al , 2014; Haag et al , 2015a) or rRNA (NSUN1/NOP2, NSUN5; Sloan et al , 2013; Tafforeau et al , 2013; Schosserer et al , 2015). NSUN2 can also modify vault RNAs and mRNAs (Hussain et al , 2013), and NSUN4 was described to localise to mitochondria where it was shown to methylate the mitochondrial 12S rRNA in mice (Cámara et al , 2011; Metodiev et al , 2014).…”

Section: Introductionmentioning

confidence: 99%

NSUN 3 and ABH 1 modify the wobble position of mt‐t RNA ^Met to expand codon recognition in mitochondrial translation

et al. 2016

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Mitochondrial gene expression uses a non‐universal genetic code in mammals. Besides reading the conventional AUG codon, mitochondrial (mt‐)tRNAM et mediates incorporation of methionine on AUA and AUU codons during translation initiation and on AUA codons during elongation. We show that the RNA methyltransferase NSUN3 localises to mitochondria and interacts with mt‐tRNAM et to methylate cytosine 34 (C34) at the wobble position. NSUN3 specifically recognises the anticodon stem loop (ASL) of the tRNA, explaining why a mutation that compromises ASL basepairing leads to disease. We further identify ALKBH1/ABH1 as the dioxygenase responsible for oxidising m5C34 of mt‐tRNAM et to generate an f5C34 modification. In vitro codon recognition studies with mitochondrial translation factors reveal preferential utilisation of m5C34 mt‐tRNA Met in initiation. Depletion of either NSUN3 or ABH1 strongly affects mitochondrial translation in human cells, implying that modifications generated by both enzymes are necessary for mt‐tRNAM et function. Together, our data reveal how modifications in mt‐tRNAM et are generated by the sequential action of NSUN3 and ABH1, allowing the single mitochondrial tRNAM et to recognise the different codons encoding methionine.

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“…References: (Cheng and Roberts, 2001;Fatemi et al, 2002;Goll et al, 2006;Kareta et al, 2006;Loenarz and Schofield, 2009) Figure 2 A simple depiction of collagen regulation, decreased levels of miRNA132 results in an increase in MeCP2 expression. MeCP2 then downregulates PPAR-γ expression ultimately causing increased collagen synthesis.…”

Section: Tet2 Tet3mentioning

confidence: 99%

DNA methylation in fibrosis

Dowson

O’Reilly

2016

European Journal of Cell Biology

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Fibrosis is characterised by an exuberant wound healing response and the major cell type responsible is the myofibroblast. The myofibroblast is typified by excessive ECM production and contractile activity and is demarcated by alpha-smooth muscle actin expression. What has recently come to light is that the activation of the fibroblast to myofibroblast may be under epigenetic control, specifically methylation. Methylation of DNA is a conserved mechanism to precisely regulate gene expression in a specific context. Hypermethylation leads to gene repression and hypomethylation results in gene induction. Methylation abnormalities have recently been uncovered in fibrosis, both organ specific and widespread fibrosis. The fact that these methylation changes are rapid and reversible lends themselves amenable to therapeutic intervention. This review considers the role of methylation in fibrosis and the activation of the myofibroblasts and how this could be targeted for fibrosis. Fibrosis is of course currently intractable to therapeutics and is a leading cause of morbidity and mortality and is an urgent unmet clinical need.

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Methylation of tRNA ^Asp by the DNA Methyltransferase Homolog Dnmt2

Cited by 1,002 publications

References 21 publications

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

NSUN 3 and ABH 1 modify the wobble position of mt‐t RNA ^Met to expand codon recognition in mitochondrial translation

DNA methylation in fibrosis

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Methylation of tRNA Asp by the DNA Methyltransferase Homolog Dnmt2

Cited by 1,002 publications

References 21 publications

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

NSUN 3 and ABH 1 modify the wobble position of mt‐t RNA Met to expand codon recognition in mitochondrial translation

DNA methylation in fibrosis

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Product

Resources

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Methylation of tRNA ^Asp by the DNA Methyltransferase Homolog Dnmt2

NSUN 3 and ABH 1 modify the wobble position of mt‐t RNA ^Met to expand codon recognition in mitochondrial translation