RDE-10/RDE-11 复合物通过与线虫中的靶 mRNA 结合触发 RNAi 诱导的 mRNA 降解。
The RDE-10/RDE-11 complex triggers RNAi-induced mRNA degradation by association with target mRNA in C. elegans.
机构信息
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
出版信息
Genes Dev. 2012 Apr 15;26(8):846-56. doi: 10.1101/gad.180679.111.
Abstract
The molecular mechanisms for target mRNA degradation in Caenorhabditis elegans undergoing RNAi are not fully understood. Using a combination of genetic, proteomic, and biochemical approaches, we report a divergent RDE-10/RDE-11 complex that is required for RNAi in C. elegans. Genetic analysis indicates that the RDE-10/RDE-11 complex acts in parallel to nuclear RNAi. Association of the complex with target mRNA is dependent on RDE-1 but not RRF-1, suggesting that target mRNA recognition depends on primary but not secondary siRNA. Furthermore, RDE-11 is required for mRNA degradation subsequent to target engagement. Deep sequencing reveals a fivefold decrease in secondary siRNA abundance in rde-10 and rde-11 mutant animals, while primary siRNA and microRNA biogenesis is normal. Therefore, the RDE-10/RDE-11 complex is critical for amplifying the exogenous RNAi response. Our work uncovers an essential output of the RNAi pathway in C. elegans.
摘要
在经历 RNAi 的秀丽隐杆线虫中，靶 mRNA 降解的分子机制尚未完全阐明。我们采用遗传、蛋白质组学和生化方法相结合的手段，报告了一种在秀丽隐杆线虫中 RNAi 所必需的、具有不同功能的 RDE-10/RDE-11 复合物。遗传分析表明，RDE-10/RDE-11 复合物与核 RNAi 平行作用。该复合物与靶 mRNA 的结合依赖于 RDE-1，但不依赖于 RRF-1，这表明靶 mRNA 的识别取决于初级而非次级 siRNA。此外，RDE-11 对于靶标结合后 mRNA 的降解是必需的。深度测序揭示 rde-10 和 rde-11 突变体动物中次级 siRNA 的丰度降低了五倍，而初级 siRNA 和 microRNA 的生物发生是正常的。因此，RDE-10/RDE-11 复合物对于扩增外源性 RNAi 反应至关重要。我们的工作揭示了秀丽隐杆线虫中 RNAi 途径的一个重要输出。
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