E-cadherin Interacts With Posttranslationally-Modified AGO2 to Enhance miRISC Activity

Jie-Ning Li; Hui-Lung Sun; Ming-Yang Wang; Pai-Sheng Chen

doi:10.3389/fcell.2021.671244

E-cadherin Interacts With Posttranslationally-Modified AGO2 to Enhance miRISC Activity

Front Cell Dev Biol. 2021 Jul 5:9:671244. doi: 10.3389/fcell.2021.671244. eCollection 2021.

Authors

Jie-Ning Li^{1

2}, Hui-Lung Sun³, Ming-Yang Wang^{4

5}, Pai-Sheng Chen^{1

2}

Affiliations

¹ College of Medicine, Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
² Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³ Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, United States.
⁴ Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
⁵ Department of Surgical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs which post-transcriptionally suppress target mRNAs expression and/or translation to modulate pathophyological processes. Expression and function of miRNAs are fine-tuned by a conserved biogenesis machinery involves two RNase-dependent processing steps of miRNA maturation and the final step of miRNA-induced silencing complex (miRISC)-mediated target silencing. A functional miRISC requires Argonaute 2 (AGO2) as an essential catalytic component which plays central roles in miRISC function. We uncovered a post-translational regulatory mechanism of AGO2 by E-cadherin. Mechanistically, E-cadherin activates ERK to phosphorylate AGO2, along with enhanced protein glycosylation. Consequently, the phosphorylated AGO2 was stabilized and ultimately resulted in induced miRISC activity on gene silencing. This study revealed a novel pathway for miRNA regulation through an E-cadherin-mediated miRISC activation.

Keywords: AGO2; E-cadherin; miRISC activity; miRNA; protein stability.