Early Developmental Exposure to dsRNA Is Critical for Initiating Efficient Nuclear RNAi in C. elegans.
Early Developmental Exposure to dsRNA Is Critical for Initiating Efficient Nuclear RNAi in C. elegans.
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DOI：
10.1016/j.celrep.2017.03.002
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发表时间：
2017-03-21
期刊：
影响因子：
8.8
通讯作者：
Hunter CP
中科院分区：
文献类型：
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作者：
Shiu PK;Hunter CP
RNA干扰（RNAi）使研究人员能够研究许多基因的功能。然而，目前还不清楚为什么有些RNAi实验成功了，而另一些却没有。在这里，我们用C表示。线虫咽肌在最初通过进食暴露于dsRNA时对RNAi具有抗性，但在下一代中对RNAi敏感。研究这一观察结果，我们发现咽肌细胞以及外阴肌细胞需要细胞核而不是细胞质RNAi。此外，我们发现在这些细胞类型中，核RNAi沉默在早期发育期间最有效地触发，从而定义了启动核RNAi的关键时期。最后，使用热休克诱导的dsRNA表达，我们表明synMuv B类突变体的作用部分地延长了这一关键窗口。synMuv B依赖的早期发育相关的启动核RNAi的关键时期表明，限制发育可塑性的机制也可能限制核RNAi的启动。
RNA interference (RNAi) has enabled researchers to study the function of many genes. However, it is not understood why some RNAi experiments succeed, while others do not. Here, we show in C. elegans that pharyngeal muscle is resistant to RNAi when initially exposed to dsRNA by feeding, but sensitive to RNAi in the next generation. Investigating this observation, we find that pharyngeal muscle cells as well as vulval muscle cells require nuclear rather than cytoplasmic RNAi. Further, we find in these cell types that nuclear RNAi silencing is most efficiently triggered during early development, defining a critical period for initiating nuclear RNAi. Finally, using heat-shock induced dsRNA expression, we show that synMuv B class mutants act in part to extend this critical window. The synMuv B-dependent early development associated critical period for initiating nuclear RNAi suggests that mechanisms that restrict developmental plasticity may also restrict the initiation of nuclear RNAi.