PDF(Pubmed)
Abstract：
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.
摘要：
小RNA测序的最新进展揭示了一个以前隐藏的调控小非编码RNA（sncRNA）的世界，它超越了研究良好的siRNA。miRNA,和piRNA。这次探索,从tRNA衍生的小RNA（tsRNAs）开始，已经导致了从各种结构的RNA（如rRNA）衍生的不同的sncRNA的发现，snoRNAs,snRNAs,YRNA,和VaultRNA，具有令人兴奋的未知功能可能性。从这个角度来看,我们讨论了超越众所周知的RNAi样机制的sncRNAs的新兴功能原理，专注于那些独立于线性序列互补性但以适体样方式起作用的序列。适体使用3D结构与配体的特异性相互作用，并受到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sncRNAs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,sncRNAs的适体样功能突出了在研究和治疗中使用小RNA模拟物的谨慎需要，因为它们的特异性不仅限于线性序列。
