The E3 ubiquitin ligase RNF114 and TAB1 degradation are required for maternal-to-zygotic transition

EMBO Rep. 2017 Feb;18(2):205-216. doi: 10.15252/embr.201642573. Epub 2017 Jan 10.

Abstract

The functional role of the ubiquitin-proteasome pathway during maternal-to-zygotic transition (MZT) remains to be elucidated. Here we show that the E3 ubiquitin ligase, Rnf114, is highly expressed in mouse oocytes and that knockdown of Rnf114 inhibits development beyond the two-cell stage. To study the underlying mechanism, we identify its candidate substrates using a 9,000-protein microarray and validate them using an in vitro ubiquitination system. We show that five substrates could be degraded by RNF114-mediated ubiquitination, including TAB1. Furthermore, the degradation of TAB1 in mouse early embryos is required for MZT, most likely because it activates the NF-κB pathway. Taken together, our study uncovers that RNF114-mediated ubiquitination and degradation of TAB1 activate the NF-κB pathway during MZT, and thus directly link maternal clearance to early embryo development.

Keywords: NF‐κB pathway; RNF114; TAB1; maternal‐to‐zygotic transition; two‐cell‐stage arrest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cluster Analysis
  • Embryonic Development / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Maternal Inheritance*
  • Mice
  • NF-kappa B / metabolism
  • Oocytes / metabolism
  • Polyubiquitin / metabolism
  • Proteolysis
  • Signal Transduction
  • Substrate Specificity
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Zygote / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • NF-kappa B
  • Tab1 protein, mouse
  • Polyubiquitin
  • Ubiquitin-Protein Ligases