Profilin2 (PFN2) is a target of the embryonic stem cell (ESC)-enriched miR-290 family of microRNAs (miRNAs) and an actin/dynamin-binding protein implicated in endocytosis. Here we show that the miR-290-PFN2 pathway regulates many aspects of ESC biology. In the absence of miRNAs, PFN2 is up-regulated in ESCs, with a resulting decrease in endocytosis. Reintroduction of miR-290, knockout of Pfn2, or disruption of the PFN2–dynamin interaction domain in miRNA-deficient cells reverses the endocytosis defect. The reduced endocytosis is associated with impaired extracellular signal-regulated kinase (ERK) signaling, delayed ESC cell cycle progression, and repressed ESC differentiation. Mutagenesis of the single canonical conserved 3′ UTR miR-290–binding site of Pfn2 or overexpression of the Pfn2 open reading frame alone in otherwise wild-type cells largely recapitulates these phenotypes. Taken together, these findings define an axis of posttranscriptional control, endocytosis, and signal transduction that is important for ESC proliferation and differentiation.

Profilin2（PFN2）是富含胚胎干细胞（ESC）的microRNA（miRNA）的miR-290家族和涉及内吞作用的肌动蛋白/动力蛋白结合蛋白的靶标。在这里，我们显示了miR-290-PFN2途径调控ESC生物学的许多方面。在不存在miRNA的情况下，PFN2在ESC中上调，导致内吞作用减少。在miRNA缺失的细胞中重新引入miR-290，敲除Pfn2或破坏PFN2-dynamin相互作用域会逆转内吞作用缺陷。减少的内吞作用与受损的细胞外信号调节激酶（ERK）信号传导，延迟的ESC细胞周期进程和抑制的ESC分化有关。Pfn2的单个经典保守3'UTR miR-290结合位点的诱变或Pfn2的过表达单独的Pfn2开放阅读框在其他野生型细胞中可以概括这些表型。综上所述，这些发现确定了转录后控制，内吞作用和信号转导的轴，这对于ESC的增殖和分化很重要。