Chen Qi, Zhou Tong
Molecular Medicine Program, University of Utah School of Medicine, Salt Lake City, Utah, USA; Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah, USA; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, Nevada, USA.
J Biol Chem. 2023 Oct;299(10):105225. doi: 10.1016/j.jbc.2023.105225. Epub 2023 Sep 9.
Recent advancements in small RNA sequencing have unveiled a previously hidden world of regulatory small noncoding RNAs (sncRNAs) that extend beyond the well-studied small interfering RNAs, microRNAs, and piwi-interacting RNAs. This exploration, starting with tRNA-derived small RNAs, has led to the discovery of a diverse universe of sncRNAs derived from various longer structured RNAs such as rRNAs, small nucleolar RNAs, small nuclear RNAs, Y RNAs, and vault RNAs, with exciting uncharted functional possibilities. In this perspective, we discuss the emerging functional principles of sncRNAs beyond the well-known RNAi-like mechanisms, focusing on those that operate independent of linear sequence complementarity but rather function in an aptamer-like fashion. Aptamers use 3D structure for specific interactions with ligands and are modulated by RNA modifications and subcellular environments. Given that aptamer-like sncRNA functions are widespread and present in species lacking RNAi, they may represent an ancient functional principle that predates RNAi. We propose a rethinking of the origin of RNAi and its relationship with these aptamer-like functions in sncRNAs and how these complementary mechanisms shape biological processes. Lastly, the aptamer-like function of sncRNAs highlights the need for caution in using small RNA mimics in research and therapeutics, as their specificity is not restricted solely to linear sequence.
小RNA测序的最新进展揭示了一个以前隐藏的调控性小非编码RNA（sncRNA）世界，其范围超出了研究充分的小干扰RNA、微小RNA和piwi相互作用RNA。从tRNA衍生的小RNA开始的这一探索，已导致发现了一个多样化的sncRNA世界，这些sncRNA源自各种更长的结构化RNA，如rRNA、小核仁RNA、小核RNA、Y RNA和穹窿体RNA，具有令人兴奋的未知功能可能性。在这篇综述中，我们讨论了sncRNA超出众所周知的RNAi样机制的新兴功能原理，重点关注那些独立于线性序列互补性起作用、而是以适体样方式发挥功能的机制。适体利用三维结构与配体进行特异性相互作用，并受RNA修饰和亚细胞环境的调节。鉴于适体样sncRNA功能广泛存在于缺乏RNAi的物种中，它们可能代表了一种早于RNAi的古老功能原理。我们建议重新思考RNAi的起源及其与sncRNA中这些适体样功能的关系，以及这些互补机制如何塑造生物过程。最后，sncRNA的适体样功能凸显了在研究和治疗中使用小RNA模拟物时需要谨慎，因为它们的特异性不仅仅局限于线性序列。
