EGO-1, a C. elegans RdRP, modulates gene expression via production of mRNA-templated short antisense RNAs.
EGO-1, a C. elegans RdRP, modulates gene expression via production of mRNA-templated short antisense RNAs.
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DOI：
10.1016/j.cub.2011.02.019
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发表时间：
2011-03-22
期刊：
影响因子：
9.2
通讯作者：
Fire, Andrew Z.
中科院分区：
文献类型：
--
作者：
Maniar, Jay M.;Fire, Andrew Z.
秀丽隐杆线虫生殖系的发育是一个复杂的过程，涉及数千个基因的协调调控。小RNA生物发生和功能所需的几个基因是生殖系正常组织所需的基因之一。EGO-1是一种假定的RNA指导的RNA聚合酶（RdRP），其是C.线虫生殖系发育和生殖系表达基因的有效RNAi。RdRP已被提出通过多种机制起作用，包括特定mRNA的转录后靶向以及通过与染色质的直接相互作用。尽管进行了广泛的研究，但EGO-1的分子作用仍然是个谜。在这里，我们使用高通量的小RNA和信使RNA测序研究EGO-1的功能。我们发现，EGO-1是需要通过几个发展阶段产生一个独特的池的小RNA反义的一些种系表达的mRNA。这些潜在的mRNA靶标分为不同的类别，包括动粒和核孔组装所需的基因、组蛋白修饰活性和着丝粒蛋白。我们还发现几个RNAi相关基因是EGO-1的靶点。最后，我们发现在ego-1（-）动物中小RNA的丢失和mRNA水平的上升之间存在强烈的关联。我们的数据支持的结论，EGO-1产生三磷酸化的小RNA来自mRNA模板，这些小RNA调节基因表达，通过其同源mRNA的靶向。
The development of the germline in Caenorhabditis elegans is a complex process involving the regulation of thousands of genes in a coordinated manner. Several genes required for small RNA biogenesis and function are among those required for the proper organization of the germline. EGO-1 is a putative RNA-directed RNA polymerase (RdRP) that is required for multiple aspects of C. elegans germline development and efficient RNAi of germline-expressed genes. RdRPs have been proposed to act through a variety of mechanisms including the post-transcriptional targeting of specific mRNAs as well as through a direct interaction with chromatin. Despite extensive investigation, the molecular role of EGO-1 has remained enigmatic. Here we use high-throughput small RNA and messenger RNA sequencing to investigate EGO-1 function. We found that EGO-1 is required to produce a distinct pool of small RNAs antisense to a number of germline-expressed mRNAs through several developmental stages. These potential mRNA targets fall into distinct classes, including genes required for kinetochore and nuclear pore assembly, histone-modifying activities and centromeric proteins. We also found several RNAi-related genes to be targets of EGO-1. Finally, we show a strong association between the loss of small RNAs and the rise of mRNA levels in ego-1(−) animals. Our data support the conclusion that EGO-1 produces triphosphorylated small RNAs derived from mRNA templates and that these small RNAs modulate gene expression through the targeting of their cognate mRNAs.
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