EGFR gets in the way of microRNA biogenesis

Abstract

Recent studies suggest that microRNA (miRNA) processing is a key regulatory step in the miRNA biogenesis as well as its transcriptional control. In a paper recently published in Nature, Shen et al. revealed that epidermal growth factor receptor (EGFR) directly interacts with argonaute 2 (AGO2), a critical component of RNA-induced silencing complex (RISC), and inhibits the maturation of specific tumor suppressive miRNAs under hypoxic condition.

Figure 1

EGFR inhibits the processing of precursor miRNA through phosphorylation of AGO2-Y393. miRNAs are transcribed from its host gene as primary miRNAs, and processed to 70-nt-long precursor miRNAs by endonuclease Drosha microprocessor complex. After active transportation to cytoplasm, Dicer, another RNase III type endonuclease, cleaves precursor miRNAs into short double-stranded RNA fragments in coordination with AGO2. Hypoxic stress induces the endocytic trafficking of EGFR into cytoplasm, where EGFR interacts with AGO2. EGFR reduces the binding of Dicer to AGO2 by phosphorylating AGO2-Y393, which results in an attenuated processing of precursor miRNAs to mature miRNAs.