Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2

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

doi:10.1126/science.1120976

Methylation of tRNA^Asp by the DNA methyltransferase homolog Dnmt2

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

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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.

Original language	English (US)
Pages (from-to)	395-398
Number of pages	4
Journal	Science
Volume	311
Issue number	5759
DOIs	https://doi.org/10.1126/science.1120976
State	Published - Jan 20 2006
Externally published	Yes

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title = "Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2",

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 (tRNAAsp) 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.",

author = "Goll, {Mary Grace} and Finn Kirpekar and Maggert, {Keith A.} and Yoder, {Jeffrey A.} and Hsieh, {Chih Lin} and Xiaoyu Zhang and Golic, {Kent G.} and Jacobsen, {Steven E.} and Bestor, {Timothy H.}",

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T1 - Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2

AU - Goll, Mary Grace

AU - Kirpekar, Finn

AU - Maggert, Keith A.

AU - Yoder, Jeffrey A.

AU - Hsieh, Chih Lin

AU - Zhang, Xiaoyu

AU - Golic, Kent G.

AU - Jacobsen, Steven E.

AU - Bestor, Timothy H.

PY - 2006/1/20

Y1 - 2006/1/20

N2 - 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 (tRNAAsp) 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.

AB - 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 (tRNAAsp) 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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Methylation of tRNA^Asp by the DNA methyltransferase homolog Dnmt2

Abstract

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