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A truncated form of dicer tilts the balance of RNA interference pathways.

Cell Rep. 2013 Aug 15;4(3):454-63. Epub 2013 Aug 08
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摘要


The RNase III enzyme Dicer is responsible for key steps in the biogenesis of small RNA species in multiple RNA interference pathways. Here, we show that, in the adult C. elegans soma, half of the total DCR-1 protein is expressed as a truncated, stable C-terminal fragment named small DCR-1 (sDCR-1). sDCR-1 operates independently of full-length DCR-1 in two distinct pathways; it enhances exogenous duanyu1615 and concurrently acts as a negative regulator of microRNA (miRNA) biogenesis. Enhancement of relies on sDCR-1 catalytic activity, whereas impinging on miRNA processing does not. Instead, sDCR-1 competes with pre-miRNA processing by interacting with the miRNA-dedicated Argonautes ALG-1 and ALG-2. Finally, triggering a strong exoduanyu1615 response in the presence of elevated levels of sDCR-1 exacerbates the miRNA processing defect. Our results unveil a surprising role for a truncated form of DCR-1 in the modulation of multiple duanyu1615 activities and in the regulation of mechanistic boundaries between pathways.

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