Therapeutic Innovation Center (THINC), Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.
Therapeutic Innovation Center (THINC), Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Cell Chem Biol. 2024 Jan 18;31(1):17-35. doi: 10.1016/j.chembiol.2023.12.010. Epub 2024 Jan 9.
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.
RNA 二级结构在编码 RNA 调控命运和功能方面发挥着重要作用。大多数 RNA 存在于多种配对状态的组合中，并通过细胞过程不断展开和折叠。测量这些结构组合及其对细胞功能的贡献一直是一个重大挑战，但新的方法和概念框架开始填补这一空白。在这篇综述中，我们提供了一个以机制和功能为中心的 RNA 二级结构组合和少数状态在调节 RNA 生命周期（从转录到降解）中的作用的纲要。我们还进一步探讨了 RNA 结构组合失调如何导致人类疾病，并讨论了用药物调节替代 RNA 状态来治疗性调节 RNA 活性的可能性。RNA 结构组合作为 RNA 功能核心的新兴范例为深入了解 RNA 生物学和新的治疗可能性提供了基础。
