Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Nat Rev Mol Cell Biol. 2019 Jan;20(1):21-37. doi: 10.1038/s41580-018-0045-7.
Since their serendipitous discovery in nematodes, microRNAs (miRNAs) have emerged as key regulators of biological processes in animals. These small RNAs form complex networks that regulate cell differentiation, development and homeostasis. Deregulation of miRNA function is associated with an increasing number of human diseases, particularly cancer. Recent discoveries have expanded our understanding of the control of miRNA function. Here, we review the mechanisms that modulate miRNA activity, stability and cellular localization through alternative processing and maturation, sequence editing, post-translational modifications of Argonaute proteins, viral factors, transport from the cytoplasm and regulation of miRNA-target interactions. We conclude by discussing intriguing, unresolved research questions.
自它们在线虫中的偶然发现以来，microRNAs（miRNAs）已成为动物生物过程的关键调节剂。这些小 RNA 形成复杂的网络，调节细胞分化、发育和内稳态。miRNA 功能的失调与越来越多的人类疾病有关，特别是癌症。最近的发现扩展了我们对 miRNA 功能控制的理解。在这里，我们综述了通过替代加工和成熟、序列编辑、Argonaute 蛋白的翻译后修饰、病毒因子、从细胞质的运输以及 miRNA-靶相互作用的调节来调节 miRNA 活性、稳定性和细胞定位的机制。最后，我们讨论了有趣但尚未解决的研究问题。
