期刊
MOLECULAR SYSTEMS BIOLOGY
卷 6, 期 -, 页码 -出版社
WILEY
DOI: 10.1038/msb.2010.89
关键词
microRNA; mRNA decay; RNAi; siRNA
资金
- Swedish Research Council
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. Molecular Systems Biology 6: 433; published online 16 November 2010; doi:10.1038/msb.2010.89
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