Computational Biology Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Mol Syst Biol. 2010 Nov 16;6:433. doi: 10.1038/msb.2010.89.
The microRNA pathway participates in basic cellular processes and its discovery has enabled the development of si/shRNAs as powerful investigational tools and potential therapeutics. Based on a simple kinetic model of the mRNA life cycle, we hypothesized that mRNAs with high turnover rates may be more resistant to RNAi-mediated silencing. The results of a simple reporter experiment strongly supported this hypothesis. We followed this with a genome-wide scale analysis of a rich corpus of experiments, including RT-qPCR validation data for thousands of siRNAs, siRNA/microRNA overexpression data and mRNA stability data. We find that short-lived transcripts are less affected by microRNA overexpression, suggesting that microRNA target prediction would be improved if mRNA turnover rates were considered. Similarly, short-lived transcripts are more difficult to silence using siRNAs, and our results may explain why certain transcripts are inherently recalcitrant to perturbation by small RNAs.
微 RNA 通路参与基本的细胞过程，其发现使 si/shRNAs 能够作为强大的研究工具和潜在的治疗方法得以发展。基于 mRNA 生命周期的简单动力学模型，我们假设周转率高的 mRNA 可能对 RNAi 介导的沉默具有更强的抗性。一个简单的报告基因实验的结果强烈支持了这一假设。我们接着对大量实验进行了全基因组规模的分析，其中包括数千个 siRNA 的 RT-qPCR 验证数据、siRNA/miRNA 过表达数据和 mRNA 稳定性数据。我们发现，短寿命的转录本受 miRNA 过表达的影响较小，这表明如果考虑 mRNA 周转率，miRNA 靶标预测将会得到改善。同样，使用 siRNA 更难使短寿命的转录本沉默，我们的结果可能解释了为什么某些转录本本质上对小 RNA 的干扰具有抗性。
