RNA secondary structure plays essential roles in encoding RNA regulatory fate and function. Most RNAs populate ensembles of alternatively paired states and are continually unfolded and refolded by cellular processes. Measuring these structural ensembles and their contributions to cellular function has traditionally posed major challenges, but new methods and conceptual frameworks are beginning to fill this void. In this review, we provide a mechanism- and function-centric compendium of the roles of RNA secondary structural ensembles and minority states in regulating the RNA life cycle, from transcription to degradation. We further explore how dysregulation of RNA structural ensembles contributes to human disease and discuss the potential of drugging alternative RNA states to therapeutically modulate RNA activity. The emerging paradigm of RNA structural ensembles as central to RNA function provides a foundation for a deeper understanding of RNA biology and new therapeutic possibilities.

中文翻译：

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RNA二级结构整体和替代状态的原因、功能和治疗可能性

RNA二级结构在编码RNA调控命运和功能中起着重要作用。大多数 RNA 都会形成交替配对状态的集合，并通过细胞过程不断展开和重新折叠。测量这些结构整体及其对细胞功能的贡献传统上提出了重大挑战，但新方法和概念框架正在开始填补这一空白。在这篇综述中，我们提供了一个以机制和功能为中心的概要，介绍了 RNA 二级结构整体和少数状态在调节 RNA 生命周期（从转录到降解）中的作用。我们进一步探讨了 RNA 结构整体的失调如何导致人类疾病，并讨论了通过药物替代 RNA 状态来治疗性调节 RNA 活性的潜力。RNA 结构整体作为 RNA 功能核心的新兴范式为更深入地了解 RNA 生物学和新的治疗可能性奠定了基础。