Dnmt2 functions in the cytoplasm to promote liver, brain, and retina development in zebrafish.
The roles of DNA methyltransferase-2 (DNMT2) enzymes are controversial; whether DNMT2 functions primarily as a nuclear DNA methyltransferase or as a cytoplasmic tRNA methyltransferase, and whether DNMT2 activity impacts development, as dnmt2 mutant mice or Drosophila lack phenotypes. Here we show that morpholino knockdown of Dnmt2 protein in zebrafish embryos confers differentiation defects in particular organs, including the retina, liver, and brain. Importantly, proper organ differentiation required Dnmt2 activity in the cytoplasm, not in the nucleus. Furthermore, zebrafish Dnmt2 methylates an RNA species of approximately 80 bases, consistent with tRNA methylation. Thus, Dnmt2 promotes zebrafish development, likely through cytoplasmic RNA methylation.
Rai
Kunal
K
Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah 84112, USA.
Chidester
Stephanie
S
Zavala
Chad V
CV
Manos
Elizabeth J
EJ
James
Smitha R
SR
Karpf
Adam R
AR
Jones
David A
DA
Cairns
Bradley R
BR
D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000196:embryology* / Q000201:enzymology; D002478:Cells, Cultured; D003593:Cytoplasm / Q000201:enzymology*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism / Q000502:physiology*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008099:Liver / Q000196:embryology* / Q000201:enzymology; D012160:Retina / Q000196:embryology* / Q000201:enzymology; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000502:physiology*
D029961:Zebrafish Proteins; D004248:DNA (Cytosine-5-)-Methyltransferases; C518283:trdmt1 protein, zebrafish