Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2.
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.
Goll
Mary Grace
MG
Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Kirpekar
Finn
F
Maggert
Keith A
KA
Yoder
Jeffrey A
JA
Hsieh
Chih-Lin
CL
Zhang
Xiaoyu
X
Golic
Kent G
KG
Jacobsen
Steven E
SE
Bestor
Timothy H
TH
D000818:Animals; D000926:Anticodon; D017360:Arabidopsis / Q000235:genetics / Q000502:physiology; D029681:Arabidopsis Proteins / Q000235:genetics; D020134:Catalytic Domain; D003596:Cytosine / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology; D019143:Evolution, Molecular; D006801:Humans; D013058:Mass Spectrometry; D008745:Methylation; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D018749:RNA, Plant / Q000378:metabolism; D012349:RNA, Transfer, Asp / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection
D000926:Anticodon; D029681:Arabidopsis Proteins; D029721:Drosophila Proteins; D018749:RNA, Plant; D012349:RNA, Transfer, Asp; D003596:Cytosine; C491786:Dnmt2 protein, mouse; C491784:Mt2 protein, Drosophila; D004248:DNA (Cytosine-5-)-Methyltransferases; C112218:TRDMT1 protein, human