Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.
Nat Rev Genet. 2021 May;22(5):307-323. doi: 10.1038/s41576-020-00309-5. Epub 2021 Jan 15.
Hundreds of microRNAs (miRNAs) are expressed in distinct spatial and temporal patterns during embryonic and postnatal mouse development. The loss of all miRNAs through the deletion of critical miRNA biogenesis factors results in early lethality. The function of each miRNA stems from their cumulative negative regulation of multiple mRNA targets expressed in a particular cell type. During development, miRNAs often coordinate the timing and direction of cell fate transitions. In adults, miRNAs frequently contribute to organismal fitness through homeostatic roles in physiology. Here, we review how the recent dissection of miRNA-knockout phenotypes in mice as well as advances related to their targets, dosage, and interactions have collectively informed our understanding of the roles of miRNAs in mammalian development and adaptive responses.
在胚胎和新生小鼠发育过程中，数百种 microRNAs（miRNAs）以独特的时空模式表达。通过删除关键 miRNA 生物发生因子，所有 miRNAs 的缺失会导致早期致死。每个 miRNA 的功能源于它们对特定细胞类型中表达的多个 mRNA 靶标的累积负调控。在发育过程中，miRNAs 经常通过协调细胞命运转变的时间和方向来发挥作用。在成年人中，miRNAs 通常通过在生理中的稳态作用来为生物体的适应性做出贡献。在这里，我们回顾了最近在小鼠中对 miRNA 敲除表型的剖析，以及与其靶标、剂量和相互作用相关的进展，这些进展共同告知了我们对 miRNA 在哺乳动物发育和适应性反应中的作用的理解。
