Kuriyama Mituhiro, Kondo Yoshinori, Tanaka Yoshiyuki
a Laboratory of Molecular Transformation, Graduate School of Pharmaceutical Sciences , Tohoku University , Sendai , Miyagi , Japan.
Nucleosides Nucleotides Nucleic Acids. 2014;33(7):466-80. doi: 10.1080/15257770.2014.887098.
Recently discovered hammerhead ribozymes that are activated through pseudoknot interactions (Watson-Crick base pairs between loops) are attractive candidates as gene-therapeutic agents because sequences of gene-therapeutic ribozymes can be designed simply based on the sequence complementarity against target RNAs. Herein, we examined if the newly found pseudoknot-type hammerhead ribozyme with type I topology is activated through the pseudoknot interactions. Substitutions of pseudoknot sequences into fully mismatched ones significantly reduced the activity of type I pseudoknot-type hammerhead ribozyme, while those with full-matched pseudoknot sequences were highly active. The results indicated that the pseudoknot interactions activated type I pseudoknot-type hammerhead ribozyme, making them suitable as gene-therapeutic agents.
最近发现的通过假结相互作用（环之间的沃森-克里克碱基对）激活的锤头状核酶，作为基因治疗剂具有吸引力，因为基因治疗核酶的序列可以简单地基于与靶RNA的序列互补性来设计。在此，我们研究了新发现的具有I型拓扑结构的假结型锤头状核酶是否通过假结相互作用被激活。将假结序列替换为完全错配的序列会显著降低I型假结型锤头状核酶的活性，而具有完全匹配假结序列的核酶则具有高活性。结果表明，假结相互作用激活了I型假结型锤头状核酶，使其适合作为基因治疗剂。
