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首页> 外文期刊>The FEBS journal >In vitro selection of adenine-dependent ribozyme against Tpl2/Cot oncogene
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In vitro selection of adenine-dependent ribozyme against Tpl2/Cot oncogene

机译：抗Tpl2 / Cot癌基因的腺嘌呤依赖性核酶的体外选择

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摘要

Hairpin ribozymes possess the properties of RNA sequence-specific recognition and site-specific cleavage. These properties make them a powerful extension of the antisense approach for the inhibition of gene expression. From a randomized RNA pool of hairpin ribozymes, using the systematic evolution of ligands by exponential enrichment, we have obtained an adenine-dependent hairpin ribozyme, Tpl2/Cot (tumour progression locus 2) ribozyme, which cleaves the Tpl2/Cot kinase mRNA sequence at nucleotides A225/G226 relative to the start codon of translation. This serine/threonine kinase activates the mitogen-activated protein kinase pathway implicated in cell proliferation in cancer. The selected 'Tpl2/Cot-YL ribozyme' efficiently cleaves its target sequence in cis and in trans; furthermore, the ribozyme efficiently cleaves a longer target sequence of 54 nucleotides in trans, as well as the full-length mRNA.
机译：发夹状核酶具有RNA序列特异性识别和位点特异性切割的特性。这些特性使它们成为反义方法抑制基因表达的有力扩展。从发夹状核酶的随机RNA池中，利用通过指数富集的配体的系统进化，我们获得了腺嘌呤依赖性发夹状核酶Tpl2 / Cot（肿瘤进展位点2）核酶，其在以下位置切割Tpl2 / Cot激酶mRNA序列相对于翻译起始密码子的核苷酸A225 / G226。该丝氨酸/苏氨酸激酶激活了与癌症细胞增殖有关的丝裂原活化的蛋白激酶途径。所选的“ Tpl2 / Cot-YL核酶”有效地以顺式和反式切割其靶序列。此外，核酶有效地切割了更长的反式54个核苷酸的靶序列以及全长mRNA。

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