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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, and Timothy H. Bestor
Science • 20 Jan 2006 • Vol 311, Issue 5759 • pp. 395-398 • DOI: 10.1126/science.1120976
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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 (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 tRNAAsp 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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We thank K. Anderson and M. Damelin for comments on the manuscript; X. Cheng for helpful discussions; and B. Berkovits, S. Chen, B. Erlanger, A. Getz, A. Kljuic, C. Köhrer, N. Papavasiliou, K. Politi, and U. RajBhandary for advice and assistance. Supported by grants from the NIH and the Danish Natural Science Research Council.

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Published In

Science
Volume 311 | Issue 5759
20 January 2006

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American Association for the Advancement of Science.

Submission history

Received: 5 October 2005
Accepted: 20 December 2005
Published in print: 20 January 2006

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Authors

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Mary Grace Goll
Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
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Finn Kirpekar
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
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Keith A. Maggert
Department of Biology, Texas A&M University, College Station, TX 77843, USA.
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Jeffrey A. Yoder
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
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Chih-Lin Hsieh
Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90089, USA.
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Xiaoyu Zhang
Howard Hughes Medical Institute (HHMI) and Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
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Kent G. Golic
Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
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Steven E. Jacobsen
Howard Hughes Medical Institute (HHMI) and Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
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Timothy H. Bestor*
Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
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Notes

* To whom correspondence should be addressed. E-mail: [email protected]

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