A structural interpretation of the effect of GC-content on efficiency of RNA interference
Background: RNA interference (RNAi) mediated by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) has become a powerful technique for eukaryotic gene knockdown.siRNA GC-content negatively correlates with RNAi efficiency, and it is of interest to have a convincing mechanistic interpretation of this observation. We here examine this issue by considering the secondary structures for both the target messenger RNA (mRNA) and the siRNA guide strand.Results: By analyzing a unique homogeneous data set of 101 shRNAs targeted to 100 endogenous human genes, we find that: 1) target site accessibility is more important than GCcontent for efficient RNAi; 2) there is an appreciable negative correlation between GCcontent and RNAi activity; 3) for the predicted structure of the siRNA guide strand, there is a lack of correlation between RNAi activity and either the stability or the number of free dangling nucleotides at an end of the structure; 4) there is a high correlation between target site accessibility and GC-content. For a set of representative structural RNAs, the GC content of 62.6% for paired bases is significantly higher than the GC content of 38.7% for unpaired bases. Thus, for a structured RNA, a region with higher GC content is likely to have more stable secondary structure. Furthermore, by partial correlation analysis, the correlation for GCcontent is almost completely diminished, when the effect of target accessibility is controlled.Conclusions: These findings provide a target-structure-based interpretation and mechanistic insight for the effect of GC-content on RNAi efficiency.
Chi Yu Chan C.Steven Carmack Dang D.Long Anil Maliyekkel Yu Shao Igor B.Roninson Ye Ding
Wadsworth Center, New York State Department of Health, 150 New Scotland Avenue, Albany, NY 12208, US Cancer Center, Ordway Research Institute, Albany, New York 12208, USA Department of Molecular Geneti Cancer Center, Ordway Research Institute, Albany, New York 12208, USA
国际会议
The 7th Asia-Pacific Bioinformatics Conference(第七届亚太生物信息学大会)
北京
英文
385-391
2009-01-01（万方平台首次上网日期，不代表论文的发表时间）