Genome-wide analysis of mRNAs regulated by Drosha and Argonaute proteins in Drosophila melanogaster
Genome-wide analysis of mRNAs regulated by Drosha and Argonaute proteins in Drosophila melanogaster
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DOI：
10.1128/mcb.26.8.2965-2975.2006
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发表时间：
2006-04-01
影响因子：
5.3
通讯作者：
Izaurralde, E
中科院分区：
文献类型：
--
作者：
Rehwinkel, J;Natalin, P;Izaurralde, E
RNA沉默途径是保守的基因调控机制，其引起与短干扰RNA和微小RNA（miRNA）互补的mRNA的衰减和/或翻译抑制。由这些途径调节的转录组的比例尚不清楚，但认为每个miRNA可能具有数百个靶标。为了在基因组水平上鉴定由沉默途径调节的转录物，我们检测了缺失四种Argonaute旁系同源物（即，AGO 1、AGO 2、PIWI或Aubergine）在RNA沉默中起重要作用。我们还分析了去除miRNA加工酶Drosha的细胞。结果表明，在Drosha耗尽的细胞中差异表达的转录物在AGO 1敲低中具有高度相关的表达，并且在预测和验证的miRNA靶中显著富集。miRNA靶点的一个子集的水平也受到AGO 2的调节。此外，AGO 1和AGO 2沉默一组共同的移动的遗传元件的表达。总之，这些结果表明，AGO 1和AGO 2在果蝇中的功能重叠比以前认为的更重要。
RNA silencing pathways are conserved gene regulation mechanisms that elicit decay and/or translational repression of mRNAs complementary to short interfering RNAs and microRNAs (miRNAs). The fraction of the transcriptome regulated by these pathways is not known, but it is thought that each miRNA may have hundreds of targets. To identify transcripts regulated by silencing pathways at the genomic level, we examined mRNA expression profiles in Drosophila melanogaster cells depleted of four Argonaute paralogs (i.e., AGO1, AGO2, PIWI, or Aubergine) that play essential roles in RNA silencing. We also profiled cells depleted of the miRNA-processing enzyme Drosha. The results reveal that transcripts differentially expressed in Drosha-depleted cells have highly correlated expression in the AGO1 knockdown and are significantly enriched in predicted and validated miRNA targets. The levels of a subset of miRNA targets are also regulated by AGO2. Moreover, AGO1 and AGO2 silence the expression of a common set of mobile genetic elements. Together, these results indicate that the functional overlap between AGO1 and AGO2 in Drosophila is more important than previously thought.