Ever since microRNAs (miRNAs) were first recognized as an extensive gene family >20 years ago, a broad community of researchers was drawn to investigate the universe of small regulatory RNAs. Although core features of miRNA biogenesis and function were revealed early on, recent years continue to uncover fundamental information on the structural and molecular dynamics of core miRNA machinery, how miRNA substrates and targets are selected from the transcriptome, new avenues for multilevel regulation of miRNA biogenesis and mechanisms for miRNA turnover. Many of these latest insights were enabled by recent technological advances, including massively parallel assays, cryogenic electron microscopy, single-molecule imaging and CRISPR–Cas9 screening. Here, we summarize the current understanding of miRNA biogenesis, function and regulation, and outline challenges to address in the future.

自从 20 多年前 microRNA (miRNA) 首次被认为是一个广泛的基因家族以来，广泛的研究人员就被吸引来研究小调控 RNA 的宇宙。尽管 miRNA 生物发生和功能的核心特征很早就被揭示，但近年来不断揭示核心 miRNA 机制的结构和分子动力学、如何从转录组中选择 miRNA 底物和靶标、miRNA 生物发生多级调控的新途径等基本信息。以及 miRNA 周转的机制。其中许多最新见解都是通过最新技术进步实现的，包括大规模并行测定、低温电子显微镜、单分子成像和 CRISPR-Cas9 筛选。在这里，我们总结了目前对 miRNA 生物发生、功能和调控的理解，并概述了未来需要解决的挑战。