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Originally published as Genetics Published Articles Ahead of Print on September 9, 2008.
Genetics, Vol. 180, 785-796, October 2008, Copyright © 2008
doi:10.1534/genetics.108.093310
ADBP-1 Regulates an ADAR RNA-Editing Enzyme to Antagonize RNA-Interference-Mediated Gene Silencing in Caenorhabditis elegans
Hiromitsu Ohta*,
Manabi Fujiwara*,1,
Yasumi Ohshima
and
Takeshi Ishihara*
* Department of Biology, Graduate School of Science, Kyushu University, Fukuoka 812-8581, Japan and Department of Applied Life Science, Faculty of Biotechnology and Life Science, Sojo University, Kumamoto 860-0082, Japan
1 Corresponding author: Department of Biology, Graduate School of Science, Kyushu University, 6-10-1, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
E-mail: mfujiscb{at}mbox.nc.kyushu-u.ac.jp
Small interfering RNAs (siRNAs) and microRNAs (miRNAs) mediate gene silencing through evolutionarily conserved pathways. In Caenorhabditis elegans, the siRNA/miRNA pathways are also known to affect transgene expression. To identify genes that regulate the efficiencies of the siRNA/miRNA pathways, we used the expression level of a transgene as an indicator of gene silencing and isolated a transgene-silencing mutant, adbp-1 (ADR-2 binding protein). The adbp-1 mutation caused transgene silencing in hypodermal and intestinal cells in a cell-autonomous manner, depending on the RNA interference (RNAi) machinery. The adbp-1 gene encodes a protein with no conserved domains that is localized in the nucleus. Yeast two-hybrid screening and co-immunoprecipitation analysis demonstrated that ADBP-1 physically interacts with ADR-2, an RNA-editing enzyme from the ADAR (adenosine deaminase acting on dsRNA) family. In the adbp-1 mutant, as previously shown in adr-2 mutants, A-to-I RNA editing was not detected, suggesting that ADBP-1 is required for the RNA-editing activity of ADR-2. We found that ADBP-1 facilitates the nuclear localization of ADR-2. ADBP-1 may regulate ADR-2 activity and the consequent RNA editing and thereby antagonize RNAi-mediated transgene silencing in C. elegans.
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