The impact of target site accessibility on the design of effective siRNAs
Small-interfering RNAs (siRNAs) assemble into RISC, the RNA-induced silencing complex, which cleaves complementary mRNAs. Despite their fluctuating efficacy, siRNAs are widely used to assess gene function. Although this limitation could be ascribed, in part, to variations in the assembly and activation of RISC, downstream events in the RNA interference (RNAi) pathway, such as target site accessibility, have so far not been investigated extensively. In this study we present a comprehensive analysis of target RNA structure effects on RNAi by computing the accessibility of the target site for interaction with the siRNA. Based on our observations, we developed a novel siRNA design tool, RNAxs, by combining known siRNA functionality criteria with target site accessibility. We calibrated our method on two data sets comprising 573 siRNAs for 38 genes, and tested it on an independent set of 360 siRNAs targeting four additional genes. Overall, RNAxs proves to be a robust siRNA selection tool that substantially improves the prediction of highly efficient siRNAs.
Democrat Barack Obama's appeal to  centrist voters has further opened the door to Republican claims his message of change only applies to the positions he has taken in the past.
AP - Iran indicated Saturday that it has no plans to meet a key Western demand that it stop enriching uranium, a day after Tehran sent the European Union a response to an international offer of incentives for halting enrichment.
AP - The call girl involved in a scandal that brought down New York's former governor has dropped a lawsuit claiming "Girls Gone Wild" founder Joe Francis exploited her image and name on the Internet.
