Mardakheh Faraz K, Shechner David M
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, UK.
Department of Pharmacology, University of Washington, Seattle, WA, USA; Institute of Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA, USA.
Cell Rep. 2025 Jul 22;44(7):115877. doi: 10.1016/j.celrep.2025.115877. Epub 2025 Jun 19.
Deciphering RNA molecules' function and regulation requires an in-depth understanding of the myriad interactions these RNAs form within their cellular environment. In this review, we present a comprehensive overview of recent technological advances that collectively form a molecular toolkit for mapping the molecular environment of RNA. We discuss innovative RNA-centric methods designed to overcome long-standing challenges in capturing direct RNA-protein interactions in living cells. Additionally, we explore transformative proximity-labeling techniques that leverage engineered enzymes and chemical catalysts to spatially resolve the composition of RNA-associated microenvironments. By critically evaluating the strengths and limitations of these emerging methodologies, we highlight how they are reshaping our understanding of RNA function, from local binding events to the dynamic organization of RNA-scaffolded compartments. These advancements not only promise to elucidate the molecular grammar underlying RNA regulatory networks in unprecedented details but also pave the way for an integrative, system-level understanding of complex RNA-mediated cellular processes.
破译RNA分子的功能和调控需要深入了解这些RNA在其细胞环境中形成的无数相互作用。在本综述中，我们全面概述了近期的技术进展，这些进展共同构成了一个用于绘制RNA分子环境的分子工具包。我们讨论了旨在克服在活细胞中捕获直接RNA-蛋白质相互作用方面长期存在的挑战而设计的创新型以RNA为中心的方法。此外，我们还探索了变革性的邻近标记技术，这些技术利用工程酶和化学催化剂在空间上解析RNA相关微环境的组成。通过批判性地评估这些新兴方法的优势和局限性，我们强调了它们如何重塑我们对RNA功能的理解，从局部结合事件到RNA支架隔室的动态组织。这些进展不仅有望以前所未有的细节阐明RNA调控网络背后的分子语法，还为对复杂的RNA介导的细胞过程进行综合的系统层面理解铺平了道路。
