The gene-silencing efficiency of siRNA is strongly dependent on the local structure of mRNA at the targeted region

被引:156
作者
Luo, KQ
Chang, DC [1 ]
机构
[1] Hong Kong Univ Sci & Technol, Dept Biol, Hong Kong, Hong Kong, Peoples R China
[2] Hong Kong Univ Sci & Technol, Dept Chem Engn, Hong Kong, Hong Kong, Peoples R China
关键词
RNA interference; RNAi; siRNA; gene silencing; mRNA structure; H-bond; Bcl-2 and cyclin B;
D O I
10.1016/j.bbrc.2004.04.027
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The gene-silencing effect of short interfering RNA (siRNA) is known to vary strongly with the targeted position of the mRNA. A number of hypotheses have been suggested to explain this phenomenon. We would like to test if this positional effect is mainly due to the secondary structure of the mRNA at the target site. We proposed that this structural factor can be characterized by a single parameter called "the hydrogen bond (H-b) index," which represents the average number of hydrogen bonds formed between nucleotides in the target region and the rest of the mRNA. This index can be determined using a computational approach. We tested the correlation between the H-b index and the gene-silencing effects on three genes (Bcl-2, hTF, and cyclin B1) using a variety of siRNAs. We found that the gene-silencing effect is inversely dependent on the H-b index, indicating that the local mRNA structure at the targeted site is the main cause of the positional effect. Based on this finding, we suggest that the H-b index can be a useful guideline for future siRNA design. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:303 / 310
页数:8
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