Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois, USA.
Nat Struct Mol Biol. 2010 Jan;17(1):24-30. doi: 10.1038/nsmb.1735. Epub 2009 Dec 27.
In Drosophila melanogaster, the small interfering RNA (siRNA) pathway is triggered by exogenous double-stranded RNA (dsRNA) or upon viral infection. This pathway requires Dicer-2 (Dcr-2) in association with a dsRNA-binding protein (dsRBP) called R2D2. A potentially distinct siRNA pathway, which requires Dcr-2 in association with a different dsRBP, called Loquacious (Loqs), is activated by endogenous dsRNA derived from transposons, structured loci and overlapping transcripts. Here we show that different sources of dsRNA enter a common siRNA pathway that requires R2D2 and Loqs. R2D2 and loqs mutants show impaired silencing triggered by injection of exogenous dsRNA or by artificial and natural expression of endogenous dsRNA. In addition, we show that these dsRBPs function sequentially and nonredundantly in collaboration with Dcr-2. Loqs is primarily required for dsRNA processing, whereas R2D2 is essential for the subsequent loading of siRNAs into effector Ago-RISC complexes.
在黑腹果蝇中，小干扰 RNA (siRNA) 途径是由外源双链 RNA (dsRNA) 或病毒感染引发的。该途径需要 Dicer-2 (Dcr-2) 与一种称为 R2D2 的 dsRNA 结合蛋白 (dsRBP) 结合。一种潜在的不同的 siRNA 途径，需要 Dcr-2 与另一种称为 Loquacious (Loqs) 的 dsRBP 结合，是由转座子、结构基因座和重叠转录本衍生的内源性 dsRNA 激活的。在这里，我们表明不同来源的 dsRNA 进入一个需要 R2D2 和 Loqs 的共同 siRNA 途径。R2D2 和 loqs 突变体显示，注射外源 dsRNA 或人工和自然表达内源性 dsRNA 引发的沉默受到损害。此外，我们表明这些 dsRBP 以顺序和非冗余的方式与 Dcr-2 合作。Loqs 主要用于 dsRNA 加工，而 R2D2 对于随后将 siRNAs 加载到效应物 Ago-RISC 复合物中是必不可少的。
