Metazoans in the DNAi Club

A chance discovery results in the first report of DNA-based gene silencing in an animal.

By | July 1, 2015

DNA INTERFERER: Just a few millimeters long, this marine tunicate, Oikopleura dioica, has provided the first glimpse into DNA interference by an animal. HIROKI NISHIDA

EDITOR'S CHOICE IN GENETICS & GENOMICS

The Paper
T. Omotezako et al., “DNA interference: DNA-induced gene silencing in the appendicularian Oikopleura dioica,” Proc R Soc B, 282:20150435, 2015.

Accidental discovery
Scientists often exploit the natural phenomenon of RNA interference (RNAi) to knock down specific genes in model organisms. Although much less common than RNAi, DNAi has been described in plants, ciliates, bacteria, and archaea. And now, thanks to an accidental finding by Tatsuya Omotezako of Osaka University, it appears that DNAi can also silence genes in a metazoan, specifically, the tiny tunicate Oikopleura dioica. “I introduced DNA fragments for another purpose,” Omotezako explained in an e-mail, but instead he found a surprising phenotype—one he would have expected from RNAi.  

As good as RNAi
To validate the hunch that DNAi was responsible for the effect, Omotezako and his colleagues microinjected fragments of the widely conserved developmental gene brachyury into O. dioica oocytes. They found tail defects in developing larvae that were indistinguishable from those induced by RNAi. Injected double-stranded DNA also reduced levels of targeted mRNA transcripts and proteins, indicating that DNAi was operating in the animal.

Finding the mechanism
The chordate has nine homologs of the protein Argonaute, which mediates RNAi in multiple plant and animal species and DNAi in a bacterium. Edze Westra, who studies Argonaute proteins at the University of Exeter, says the next clear step is to knock down those homologs, if possible, to validate the biological relevance of DNAi in O. dioica.

A handy tool
“Preparing DNA fragments is much easier, faster, and less expensive than preparing [double-stranded] RNA for RNAi,” says Omotezako. His lab is already taking advantage of DNAi to study O. dioica development while working to figure out the mechanism behind it.

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