Kim Haedong, Lee Young-Yoon, Kim V Narry
Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea.
School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
Nat Rev Mol Cell Biol. 2025 Apr;26(4):276-296. doi: 10.1038/s41580-024-00805-0. Epub 2024 Dec 19.
MicroRNAs (miRNAs) are small, yet profoundly influential, non-coding RNAs that base-pair with mRNAs to induce RNA silencing. Although the basic principles of miRNA biogenesis and function have been established, recent breakthroughs have yielded important new insights into the molecular mechanisms of miRNA biogenesis. In this Review, we discuss the metazoan miRNA biogenesis pathway step-by-step, focusing on the key biogenesis machinery, including the Drosha-DGCR8 complex (Microprocessor), exportin-5, Dicer and Argonaute. We also highlight newly identified cis-acting elements and their impact on miRNA maturation, informed by advanced high-throughput and structural studies, and discuss recently discovered mechanisms of clustered miRNA processing, target recognition and target-directed miRNA decay (TDMD). Lastly, we explore multiple regulatory layers of miRNA biogenesis, mediated by RNA-protein interactions, miRNA tailing (uridylation or adenylation) and RNA modifications.
微小RNA（miRNA）是一类短小却具有深远影响力的非编码RNA，它们与信使核糖核酸（mRNA）通过碱基互补配对来诱导RNA沉默。尽管miRNA生物合成及功能的基本原理已被确立，但近期的突破为miRNA生物合成的分子机制带来了重要的新见解。在本综述中，我们逐步探讨后生动物miRNA生物合成途径，重点关注关键的生物合成机制，包括Drosha-DGCR8复合物（微处理器）、核输出蛋白5、Dicer和AGO蛋白。我们还强调了新发现的顺式作用元件及其对miRNA成熟的影响，这些是基于先进的高通量和结构研究得出的，并讨论了最近发现的成簇miRNA加工、靶标识别和靶标导向的miRNA降解（TDMD）机制。最后，我们探讨了由RNA-蛋白质相互作用、miRNA加尾（尿苷酸化或腺苷酸化）和RNA修饰介导的miRNA生物合成的多个调控层面。
