Mammalian hyperplastic discs Homolog EDD Regulates miRNA-Mediated Gene Silencing

Hong Su, Shuxia Meng, Yanyan Lu, Melanie I. Trombly, Jian Chen, Chengyi Lin, Anita Turk, Xiaozhong Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

MicroRNAs (miRNAs) regulate gene expression through translation repression and mRNA destabilization. However, the molecular mechanisms of miRNA silencing are still not well defined. Using a genetic screen in mouse embryonic stem (ES) cells, we identify mammalian hyperplastic discs protein EDD, a known E3 ubiquitin ligase, as a key component of the miRNA silencing pathway. ES cells deficient for EDD are defective in miRNA function and exhibit growth defects. We demonstrate that E3 ubiquitin ligase activity is dispensable for EDD function in miRNA silencing. Instead, EDD interacts with GW182 family proteins in the Argonaute-miRNA complexes. The PABC domain of EDD is essential for its silencing function. Through the PABC domain, EDD participates in miRNA silencing by recruiting downstream effectors. Among the PABC-interactors, DDX6 and Tob1/2 are both required and sufficient for silencing mRNA targets. Taken together, these data demonstrate a critical function for EDD in miRNA silencing.

Original languageEnglish (US)
Pages (from-to)97-109
Number of pages13
JournalMolecular cell
Volume43
Issue number1
DOIs
StatePublished - Jul 8 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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