Drosophila R2D2 mediates follicle formation in somatic tissues through interactions with Dicer-1
Drosophila R2D2 mediates follicle formation in somatic tissues through interactions with Dicer-1
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DOI：
10.1016/j.mod.2008.01.006
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发表时间：
2008-05-01
影响因子：
2.6
通讯作者：
Smith, Dean P.
中科院分区：
文献类型：
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作者：
Kalidas, Savitha;Sanders, Charcacia;Smith, Dean P.
miRNA 通路已被证明可以调节发育中重要的基因。 Dicer-1 需要将内源编码的 microRNA (miRNA) 前体切割成调节内源基因表达的成熟 miRNA。 RNA 干扰 (RNAi) 是一种由双链 RNA (dsRNA) 触发的基因沉默机制，可保护生物体免受寄生核酸的侵害。在果蝇中，Dicer-2 将 dsRNA 切割成 21 个碱基对的小干扰 RNA (siRNA)，将其加载到 RISC（RNA 诱导沉默复合物）中，RISC 又切割与 siRNA 同源的 mRNA。 Dicer-2 与 R2D2 共同纯化，R2D2 是一种低分子量蛋白质，可将 siRNA 加载到 RISC 中的 Ago-2 上。 R2D2 的缺失会导致 RNAi 缺陷。然而，与 Dicer-2 或 Ago-2 等其他 RNAi 成分的突变体不同，我们在此报告 r2d2(1) 突变体具有显着的发育缺陷。 r2d21 突变体降低了女性的生育能力，产生的后代数量不到正常数量的 1/10。这些逃逸者具有正常的形态。我们展示了 R2D2 在卵巢中的功能，特别是在产生茎和其他卵泡细胞的体细胞组织中，这些细胞对于建立卵母细胞的细胞结构至关重要。最有趣的是，当 dcr-1 基因的一个拷贝缺失并且 Dicer-1 蛋白与 R2D2 抗血清共免疫沉淀时，女性生育力缺陷会显着增强。这些数据表明，r2d21 突变体由于卵泡细胞功能异常而导致活力降低和女性生育力缺陷，而 Dicer-1 会影响这一过程。我们得出的结论是，R2D2 的功能超出了 RNA 干扰的作用，还包括果蝇卵巢的发育。 (c) 2008 Elsevier Ireland Ltd. 保留所有权利。
The miRNA pathway has been shown to regulate developmentally important genes. Dicer-1 is required to cleave endogenously encoded microRNA (miRNA) precursors into mature miRNAs that regulate endogenous gene expression. RNA interference (RNAi) is a gene silencing mechanism triggered by double-stranded RNA (dsRNA) that protects organisms from parasitic nucleic acids. In Drosophila, Dicer-2 cleaves dsRNA into 21 base-pair small interfering RNA (siRNA) that are loaded into RISC (RNA induced silencing complex) that in turn cleaves mRNAs homologous to the siRNAs. Dicer-2 co-purifies with R2D2, a low-molecular weight protein that loads siRNA onto Ago-2 in RISC. Loss of R2D2 results in defective RNAi. However, unlike mutants in other RNAi components like Dicer-2 or Ago-2, we report here that r2d2(1) mutants have striking developmental defects. r2d21 mutants have reduced female fertility, producing less than 1/10 the normal number of progeny. These escapers have normal morphology. We show R2D2 functions in the ovary, specifically in the somatic tissues giving rise to the stalk and other follicle cells critical for establishing the cellular architecture of the oocyte. Most interestingly, the female fertility defects are dramatically enhanced when one copy of the dcr-1 gene is missing and Dicer-1 protein co-immunoprecipitates with R2D2 antisera. These data show that r2d21 mutants have reduced viability and defective female fertility that stems from abnormal follicle cell function, and Dicer-1 impacts this process. We conclude that R2D2 functions beyond its role in RNA interference to include ovarian development in Drosophila. (c) 2008 Elsevier Ireland Ltd. All rights reserved.