Lipid-mediated phase separation of AGO proteins on the ER controls nascent-peptide ubiquitination

• DOI: 10.1016/j.molcel.2022.02.035
• Publication Date: 2022-03-23T14:33:10Z
• Authors: Yajie Gao; Yuanxiang Zhu; Hailong Wang; Ying Cheng; Dongbo Zhao; Qinmiao Sun; Dahua Chen
• Keywords: Endoplasmic-reticulum-associated protein degradation; Ubiquitin-conjugating enzyme

AGO/miRNA-mediated gene silencing and ubiquitin-mediated protein quality control represent two fundamental mechanisms that proper expression. Here, we unexpectedly discover fly human AGO proteins, which are key components in the miRNA pathway, undergo lipid-mediated phase separation condense into RNP granules on endoplasmic reticulum (ER) membrane to production. Phase ER is mediated by electrostatic interactions between a conserved lipid-binding motif within AGOs lipid PI(4,5)P2. The ER-localized condensates recruit E3 ubiquitin ligase Ltn1 catalyze nascent-peptide ubiquitination coordinate with VCP-Ufd1-Npl4 complex process unwanted products for proteasomal degradation. Collectively, our study provides insight understanding of post-transcription-translation coupling controlled via separation.