Dead end1 is an essential partner of NANOS2 for selective binding of target RNAs in male germ cell development

EMBO Rep. 2016 Jan;17(1):37-46. doi: 10.15252/embr.201540828. Epub 2015 Nov 20.

Abstract

RNA-binding proteins (RBPs) play important roles for generating various cell types in many developmental processes, including eggs and sperms. Nanos is widely known as an evolutionarily conserved RNA-binding protein implicated in germ cell development. Mouse NANOS2 interacts directly with the CCR4-NOT (CNOT) deadenylase complex, resulting in the suppression of specific RNAs. However, the mechanisms involved in target specificity remain elusive. We show that another RBP, Dead end1 (DND1), directly interacts with NANOS2 to load unique RNAs into the CNOT complex. This interaction is mediated by the zinc finger domain of NANOS2, which is essential for its association with target RNAs. In addition, the conditional deletion of DND1 causes the disruption of male germ cell differentiation similar to that observed in Nanos2-KO mice. Thus, DND1 is an essential partner for NANOS2 that leads to the degradation of specific RNAs. We also present the first evidence that the zinc finger domain of Nanos acts as a protein-interacting domain for another RBP, providing a novel insight into Nanos-mediated germ cell development.

Keywords: Dead end; Nanos; RNA; germ cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Cell Differentiation*
  • Embryonic Germ Cells / cytology
  • Embryonic Germ Cells / physiology*
  • Gene Expression Regulation, Developmental
  • Male
  • Mice, Knockout
  • Neoplasm Proteins / deficiency
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Protein Interaction Domains and Motifs
  • RNA / metabolism*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Spermatozoa / physiology
  • Zinc Fingers / physiology

Substances

  • Carrier Proteins
  • Dnd1 protein, mouse
  • Nanos2 protein, mouse
  • Neoplasm Proteins
  • RNA-Binding Proteins
  • RNA