siRNA target site secondary structure predictions using local stable substructures.
siRNA target site secondary structure predictions using local stable substructures.
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DOI：
10.1093/nar/gni026
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发表时间：
2005-02-18
影响因子：
14.9
通讯作者：
Rossi JJ
中科院分区：
文献类型：
--
作者：
Heale BS;Soifer HS;Bowers C;Rossi JJ
基于晶体结构的Ago2催化中心模型表明，siRNA和mRNA必须能够形成a -螺旋，才能正确定位可剪切的磷酸键，从而在RNAi中进行裂解。这表明目标mRNA与自身的碱基配对，即二级结构，必须在切割前去除。在siRNA设计的早期，富含gc的目标位点被避免，因为它们有可能参与强二级结构。mRNA二级结构在RNAi中的重要性尚不清楚。然而，已经确定的是，siRNA双链末端的热稳定性差异决定了哪条链被装载到rna诱导的沉默复合物中。在这里，我们使用一种新的二级结构预测方法和双端微分计算来研究二级结构在siRNA设计中的重要性。我们发现，在所检测的80个siRNA位点中，仅差异双端稳定性就可以预测60%的功能，并且二级结构预测可以提高对位点功效的预测。使用二级结构预测和双端微分法可以消除总共80%的非功能位点。
The crystal structure based model of the catalytic center of Ago2 revealed that the siRNA and the mRNA must be able to form an A-helix for correct positing of the scissile phosphate bond for cleavage in RNAi. This suggests that base pairing of the target mRNA with itself, i.e. secondary structure, must be removed before cleavage. Early on in the siRNA design, GC-rich target sites were avoided because of their potential to be involved in strong secondary structure. It is still unclear how important a factor mRNA secondary structure is in RNAi. However, it has been established that a difference in the thermostability of the ends of an siRNA duplex dictate which strand is loaded into the RNA-induced silencing complex. Here, we use a novel secondary structure prediction method and duplex-end differential calculations to investigate the importance of a secondary structure in the siRNA design. We found that the differential duplex-end stabilities alone account for functional prediction of 60% of the 80 siRNA sites examined, and that secondary structure predictions improve the prediction of site efficacy. A total of 80% of the non-functional sites can be eliminated using secondary structure predictions and duplex-end differential.
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影响因子：
11.4
作者：
Elbashir, SM;Martinez, J;Tuschl, T
通讯作者：
Tuschl, T
DOI：
10.1089/108729003768247619
发表时间：
2003-01-01
期刊：
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT
影响因子：
--
作者：
Kim, DH;Rossi, JJ
通讯作者：
Rossi, JJ
影响因子：
16.8
作者：
Haley, B;Zamore, PD
通讯作者：
Zamore, PD
影响因子：
11.4
作者：
Le Hir, H;Izaurralde, E;Moore, MJ
通讯作者：
Moore, MJ
影响因子：
4.5
作者：
Custódio, N;Carvalho, C;Carmo-Fonseca, M
通讯作者：
Carmo-Fonseca, M