Regulation of GVBD in mouse oocytes by miR-125a-3p and Fyn kinase through modulation of actin filaments

Sci Rep. 2017 May 22;7(1):2238. doi: 10.1038/s41598-017-02071-x.

Abstract

Meiotically arrested oocytes are characterized by the presence of the nuclear structure known as germinal-vesicle (GV), the breakdown of which (GVBD) is associated with resumption of meiosis. Fyn is a pivotal factor in resumption of the first meiotic division; its inhibition markedly decreases the fraction of oocytes undergoing GVBD. Here, we reveal that in mouse oocytes Fyn is post-transcriptionally regulated by miR-125a-3p. We demonstrate that in oocytes resuming meiosis miR-125a-3p and Fyn exhibit a reciprocal expression pattern; miR-125a-3p decreases alongside with an increase in Fyn expression. Microinjection of miR-125a-3p inhibits GVBD, an effect that is markedly reduced by Fyn over-expression, and impairs the organization of the actin rim surrounding the nucleus. Lower rate of GVBD is also observed in oocytes exposed to cytochalasin-D or blebbistatin, which interfere with actin polymerization and contractility of actin bundles, respectively. By down-regulating Fyn in HEK-293T cells, miR-125a-3p reduces the interaction between actin and A-type lamins, which constitute the nuclear-lamina. Our findings suggest a mechanism, by which a decrease in miR-125a-3p during oocyte maturation facilitates GVBD by allowing Fyn up-regulation and the resulting stabilization of the interaction between actin and A-type lamins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / genetics*
  • Actins / metabolism
  • Analysis of Variance
  • Animals
  • Cell Differentiation / genetics
  • Cell Nucleus / genetics*
  • Cell Nucleus / metabolism*
  • Female
  • Gene Expression Regulation
  • Humans
  • Meiosis*
  • Mice
  • MicroRNAs / genetics*
  • Oocytes / cytology
  • Oocytes / metabolism*
  • Protein Multimerization
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins c-fyn / genetics*
  • Proto-Oncogene Proteins c-fyn / metabolism
  • RNA Interference

Substances

  • Actins
  • MicroRNAs
  • Mirn125 microRNA, mouse
  • Fyn protein, mouse
  • Proto-Oncogene Proteins c-fyn