Members of the miR-290 family are the most abundantly expressed microRNAs (miRNAs) in mouse embryonic stem cells (ESCs). They regulate aspects of differentiation, pluripotency, and proliferation of ESCs, but the molecular program that they control has not been fully delineated. In the absence of Dicer, ESCs fail to express mature miR-290 miRNAs and have selective aberrant overexpression of Hoxa, Hoxb, Hoxc, and Hoxd genes essential for body plan patterning during embryogenesis, but they do not undergo a full differentiation program. Introduction of mature miR-291 into DCR^−/− ESCs restores Hox gene silencing. This was attributed to the unexpected regulation of Polycomb-mediated gene targeting by miR-291. We identified the methyltransferase Ash1l as a pivotal target of miR-291 mediating this effect. Collectively, our data shed light on the role of Dicer in ESC homeostasis by revealing a facet of molecular regulation by the miR-290 family.

miR-290家族的成员是小鼠胚胎干细胞（ESC）中表达最丰富的microRNA（miRNA）。它们调节ESC的分化，多能性和增殖的方面，但是它们所控制的分子程序尚未完全描述。在没有Dicer的情况下，ESC无法表达成熟的miR-290 miRNA ，并且在胚胎发生过程中对人体计划模式必不可少的Hoxa，Hoxb，Hoxc和Hoxd基因有选择性的异常过表达，但它们没有经过完整的分化程序。将成熟的miR-291引入DCR ^-/- ESC可恢复Hox基因沉默。这归因于miR-291对Polycomb介导的基因靶向的意外调控。我们确定甲基转移酶Ash111是介导这种作用的miR-291的关键目标。总之，我们的数据通过揭示miR-290家族分子调控的一个方面，揭示了Dicer在ESC稳态中的作用。