Comparative analysis of argonaute-dependent small RNA pathways in Drosophila.

Comparative analysis of argonaute-dependent small RNA pathways in Drosophila.
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DOI:
10.1016/j.molcel.2008.10.018
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发表时间:
2008-11-21
期刊:
影响因子:
16
通讯作者:
Hannon, Gregory J.
Hannon, Gregory J.
中科院分区:
生物学1区
文献类型:
--
作者:
Zhou, Rui;Hotta, Ikuko;Denli, Ahmet M.;Hong, Pengyu;Perrimon, Norbert;Hannon, Gregory J.

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RNAi 途径的特异性由几类小 RNA 决定,包括 siRNA、piRNA、endo-siRNA 和 microRNA (miRNA)。这些小 RNA 总是被整合到含有 Argonaute (Ago) 的大型效应复合物中,称为 RNA 诱导沉默复合物 (RISC),它们引导该复合物沉默靶标。遗传和生化策略都产生了小 RNA 生物发生和效应机制的保守分子成分。然而,考虑到这些途径的复杂性,可能还有其他成分和监管机构有待发现。我们进行了比较和全面的 RNAi 筛选,以确定影响果蝇 S2 细胞中三个主要 Ago 依赖性小 RNA 途径的基因。我们确定了在 siRNA、endo-siRNA 和 miRNA 途径中发挥积极或消极作用的候选者子集。我们的研究表明,所有三个 Argonaute 依赖性沉默途径共有许多成分,尽管每个途径也受到离散基因组的影响。
The specificity of RNAi pathways is determined by several classes of small RNAs, which include siRNAs, piRNAs, endo-siRNAs, and microRNAs (miRNAs). These small RNAs are invariably incorporated into large Argonaute (Ago)-containing effector complexes known as RNA-induced silencing complexes (RISCs), which they guide to silencing targets. Both genetic and biochemical strategies have yielded conserved molecular components of small RNA biogenesis and effector machineries. However, given the complexity of these pathways, there are likely to be additional components and regulators that remain to be uncovered. We have undertaken a comparative and comprehensive RNAi screen to identify genes that impact three major Ago-dependent small RNA pathways that operate in Drosophila S2 cells. We identify subsets of candidates that act positively or negatively in siRNA, endo-siRNA and miRNA pathways. Our studies indicate that many components are shared among all three Argonaute-dependent silencing pathways, though each is also impacted by discrete sets of genes.
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