Tdrd3 regulates the progression of meiosis II through translational control of Emi2 mRNA in mouse oocytes

Abstract

After completion of meiosis I, the oocyte immediately enters meiosis II and forms a metaphase II (MII) spindle without an interphase, which is fundamental for generating a haploid gamete. Here, we identify tudor domain-containing protein 3 (Tdrd3) as a novel regulator of oocyte meiosis. Although early mitotic inhibitor 2 (Emi2) protein has been shown to ensure the meiosis I to II transition and the subsequent MII spindle formation by inhibiting the anaphase-promoting complex/cyclosome (APC/C), how it accumulates after meiosis I has remained unresolved. We isolated Tdrd3 as a protein binding specifically and directly to Emi2 mRNA. In GV-stage mouse oocytes, Emi2 mRNA assembled into RNA granules containing Tdrd3, while cyclin B1 mRNA, which was translated in early meiosis I, formed different granules. Knockdown of Tdrd3 attenuated Emi2 synthesis in meiosis II without affecting cyclin B1 synthesis in meiosis I. Moreover, Tdrd3-deficient oocytes entered interphase and failed to form an MII spindle after completion of meiosis I. These defects were rescued by GFP-Emi2 expressed after meiosis I. Taken together, our results demonstrate the importance of Tdrd3-mediated translational control of Emi2 mRNA, which promotes Emi2 synthesis in meiosis II, for the progression of meiosis. • Emi2 accumulates in meiosis II by temporally controlled mRNA translation. • Dormant cyclin B1 and Emi2 mRNAs assemble into different granules in mouse oocytes. • cyclin B1 and Emi2 RNA granules consist of common and specific components. • Tdrd3 colocalizes with Emi2 RNA granules and controls mRNA translation in meiosis II. • Tdrd3-mediated Emi2 translation promotes the progression of meiosis II.