Li, Jie-NingJie-NingLiSun, Hui-LungHui-LungSunMING-YANG WANGChen, Pai-ShengPai-ShengChen2021-09-142021-09-1420212296-634Xhttps://scholars.lib.ntu.edu.tw/handle/123456789/582713MicroRNAs (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.enAGO2; E-cadherin; miRISC activity; miRNA; protein stabilityjournal article10.3389/fcell.2021.671244342910462-s2.0-85110640277https://api.elsevier.com/content/abstract/scopus_id/85110640277