Methylation of tRNAAsp by the DNA Methyltransferase Homolog Dnmt2 (Science, 2006, 311:395-398)

報告日期: 2006/04/14
報告時間: 15:10/16:00
報告學生: 楊瑞珠
講評老師: 張文粲
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Methylation of tRNAAsp by the DNA

Methyltransferase Homolog Dnmt2

Science 311: 395 – 398 (2006)

 

Speaker: 楊瑞珠                  Time: 14/4/2006 15:10~16:00

Commentator: 張文粲 老師         Place Room: 602

 

Abstract:

    Epigenetic inactivation of genes that are crucial for controlling normal cell growth is a hallmark of cancer cells. Among those epigenetic mechanisms, DNA methylation is the only one that could modify DNA directly. DNA methylation is mediated by a conserved group of proteins called DNA (cytosine-5) methyltransferases (DNMTs) including DNMT2. DNMT2 contains all the catalytic motifs necessary for cytosine methyltransferases and its structure is very similar to prokaryotic DNA methyltransferases; however, the biological function of DNMT2 family is still unclear. In this study, the authors found that human DNMT2 (hDNMT2) is primarily localized in the cytoplasm of mouse 3T3 fibroblasts. This argues the expected function in DNA methylation of hDNMT2. The authors then tested whether hDNMT2 has the ability to transfer tritium-labeled methyl groups to genomic DNA and RNA purified from wild-type or Dnmt2-/- mice. Surprisingly, instead of working on DNA, they found that hDNMT2 could specifically methylate a small RNA molecule, the aspartic acid transfer RNA (tRNAAsp). The methylation site on tRNAAsp at cytosine 38 in the anticodon loop was observed by mass spectrometry. Loss of a single methyl group caused an increase in electrophoretic mobility of tRNAAsp, which could be restored by hDNMT2. In addition, the authors also demonstrated that the function of DNMT2 is dependent on the preexisting modifications on the tRNAAsp. Analysis of tRNAAsp showed sequences invariantly among organisms that contain Dnmt2. In conclusion, the authors demonstrated that DNMT2 is a RNA methyltransferase. Based on these results, the authors raised a novel possibility that eukaryotic DNA methyltransferases may derive from Dnmt2-like RNA methyltransferases.

 

References:

1. Goll, M. G., and Bestor, T. H. (2005). Eukaryotic cytosine methyltransferases. Annu Rev Biochem 74, 481-514.

2. Yoder, J. A., and Bestor, T. H. (1998). A candidate mammalian DNA methyltransferase related to pmt1p of fission yeast. Hum Mol Genet 7, 279-284.