MicroRNA-dependent Inhibition of PFN2 Orchestrates ERK Activation and Pluripotent State Transitions by Regulating Endocytosis

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2020 Aug 14

PMID 32788350

Citations 4

Authors

Carolyn Sangokoya

Robert Blelloch

Affiliations

Soon will be listed here.

Abstract

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 , 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 or overexpression of the 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.

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