Scientific Reports (May 2017)

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

  • Hadas Grossman,
  • Efrat Har-Paz,
  • Natalie Gindi,
  • Mattan Levi,
  • Irit Miller,
  • Nava Nevo,
  • Dalia Galiani,
  • Nava Dekel,
  • Ruth Shalgi

DOI
https://doi.org/10.1038/s41598-017-02071-x
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 15

Abstract

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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.