Dnmt2 functions in the cytoplasm to promote liver, brain, and retina development in zebrafish

  1. Kunal Rai1,2,3,
  2. Stephanie Chidester2,
  3. Chad V. Zavala2,
  4. Elizabeth J. Manos2,
  5. Smitha R. James5,
  6. Adam R. Karpf5,
  7. David A. Jones2,3,4,7, and
  8. Bradley R. Cairns1,2,3,6
  1. 1 Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah 84112, USA;
  2. 2 Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA;
  3. 3 Department of Oncological Sciences, University of Utah, Salt Lake City, Utah 84112, USA;
  4. 4 Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, USA;
  5. 5 Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, 14263, USA

Abstract

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 ∼80 bases, consistent with tRNA methylation. Thus, Dnmt2 promotes zebrafish development, likely through cytoplasmic RNA methylation.

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  1. doi: 10.1101/gad.1472907 Genes & Dev. 21: 261-266 Copyright © 2007, Cold Spring Harbor Laboratory Press

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