Main content area

RNA helicase Belle/DDX3 regulates transgene expression in Drosophila

Lo, Pang-Kuo, Huang, Yi-Chun, Poulton, John S., Leake, Nicholas, Palmer, William H., Vera, Daniel, Xie, Gengqiang, Klusza, Stephen, Deng, Wu-Min
Developmental biology 2016 v.412 pp. 57-70
DEAD-box RNA helicases, Drosophila, RNA interference, biogenesis, chromatin, female fertility, gene expression, germ cells, humans, microRNA, mutants, mutation, oogenesis, phenotype, small interfering RNA, transgenes, yeasts
Belle (Bel), the Drosophila homolog of the yeast DEAD-box RNA helicase DED1 and human DDX3, has been shown to be required for oogenesis and female fertility. Here we report a novel role of Bel in regulating the expression of transgenes. Abrogation of Bel by mutations or RNAi induces silencing of a variety of P-element-derived transgenes. This silencing effect depends on downregulation of their RNA levels. Our genetic studies have revealed that the RNA helicase Spindle-E (Spn-E), a nuage RNA helicase that plays a crucial role in regulating RNA processing and PIWI-interacting RNA (piRNA) biogenesis in germline cells, is required for loss-of-bel-induced transgene silencing. Conversely, Bel abrogation alleviates the nuage-protein mislocalization phenotype in spn-E mutants, suggesting a competitive relationship between these two RNA helicases. Additionally, disruption of the chromatin remodeling factor Mod(mdg4) or the microRNA biogenesis enzyme Dicer-1 (Dcr-1) also alleviates the transgene-silencing phenotypes in bel mutants, suggesting the involvement of chromatin remodeling and microRNA biogenesis in loss-of-bel-induced transgene silencing. Finally we show that genetic inhibition of Bel function leads to de novo generation of piRNAs from the transgene region inserted in the genome, suggesting a potential piRNA-dependent mechanism that may mediate transgene silencing as Bel function is inhibited.