The wide prevalence and regulated expression of long non-coding RNAs (lncRNAs) highlight their functional roles, but the molecular basis for their activity and structure-function relationships remain to be investigated, with few exceptions. Among the relatively few lncRNAs conserved over significant evolutionary distances is the long intergenic non-coding RNA (lincRNA) Cyrano (orthologous to human OIP5-AS1), which contains a region of 300 highly conserved nucleotides within tetrapods, which in turn contains a functional stretch of 26 nucleotides of deep conservation. This region binds to and facilitates the degradation of the microRNA miR-7, a short ncRNA with multiple cellular functions, including modulation of oncogenic expression. We probed the secondary structure of Cyrano in vitro and in cells using chemical and enzymatic probing, and validated the results using comparative sequence analysis. At the center of the functional core of Cyrano is a cloverleaf structure maintained over the >400 million years of divergent evolution that separate fish and primates. This strikingly conserved motif provides interaction sites for several RNA-binding proteins and masks a conserved recognition site for miR-7. Conservation in this region strongly suggests that the function of Cyrano depends on the formation of this RNA structure, which could modulate the rate and efficiency of degradation of miR-7.

中文翻译：

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lincRNA Cyrano 功能核心中进化保守的 RNA 结构

长链非编码 RNA (lncRNAs) 的广泛流行和调控表达突出了它们的功能作用，但除少数例外外，它们的活性和结构-功能关系的分子基础仍有待研究。在相对少数的在显着进化距离上保守的 lncRNA 中，有长基因间非编码 RNA (lincRNA) Cyrano（与人类 OIP5-AS1 直系同源），它在四足动物中包含 300 个高度保守的核苷酸区域，而后者又包含一个功能性延伸26 个核苷酸的深度保护。该区域与 microRNA miR-7 结合并促进其降解，这是一种具有多种细胞功能的短 ncRNA，包括调节致癌基因表达。我们使用化学和酶促探测在体外和细胞中探测了 Cyrano 的二级结构，并使用比较序列分析验证结果。Cyrano 功能核心的中心是一个三叶草结构，该结构在超过 4 亿年的分化进化中保持，将鱼类和灵长类动物分开。这种极其保守的基序为几种 RNA 结合蛋白提供了相互作用位点，并掩盖了 miR-7 的保守识别位点。该区域的保守性强烈表明，Cyrano 的功能取决于这种 RNA 结构的形成，这可以调节 miR-7 的降解速率和效率。这种极其保守的基序为几种 RNA 结合蛋白提供了相互作用位点，并掩盖了 miR-7 的保守识别位点。该区域的保守性强烈表明，Cyrano 的功能取决于这种 RNA 结构的形成，这可以调节 miR-7 的降解速率和效率。这个惊人的保守基序为几种 RNA 结合蛋白提供了相互作用位点，并掩盖了 miR-7 的保守识别位点。该区域的保守性强烈表明，Cyrano 的功能取决于这种 RNA 结构的形成，这可以调节 miR-7 的降解速率和效率。