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Science 20 January 2006:
Vol. 311. no. 5759, pp. 395 - 398
DOI: 10.1126/science.1120976
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Reports

Methylation of tRNAAsp by the DNA Methyltransferase Homolog Dnmt2

Mary Grace Goll,1 Finn Kirpekar,2 Keith A. Maggert,3 Jeffrey A. Yoder,4 Chih-Lin Hsieh,5 Xiaoyu Zhang,6 Kent G. Golic,7 Steven E. Jacobsen,6 Timothy H. Bestor1*

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.

1 Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
2 Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
3 Department of Biology, Texas A&M University, College Station, TX 77843, USA.
4 Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
5 Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90089, USA.
6 Howard Hughes Medical Institute (HHMI) and Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
7 Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.

* To whom correspondence should be addressed. E-mail: THB12{at}Columbia.edu

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