The RNA ligase RNA terminal phosphate cyclase B regulates mRNA alternative splicing and is required for mouse oocyte development and maintenance.

Recent large-scale mRNA sequencing has shown that introns are retained in 5-10% of mRNA, and these events are named intron retention (IR). IR has been recognized as a key mechanism in the regulation of gene expression. However, the role of this mechanism in female reproduction in mammals remains unclear.

Oocyte meiosis-coupled poly(A) polymerase α phosphorylation and activation trigger maternal mRNA translation in mice.

Mammalian oocyte maturation is driven by strictly regulated polyadenylation and translational activation of maternal mRNA stored in the cytoplasm. However, the poly(A) polymerase (PAP) that directly mediates cytoplasmic polyadenylation in mammalian oocytes has not been determined. In this study, we identified PAPα as the elusive enzyme that catalyzes cytoplasmic mRNA polyadenylation implicated in mouse oocyte maturation.

Positive Feedback Stimulation of and mRNA Translation by MAPK Cascade During Mouse Oocyte Maturation.

In mammalian species, both the maturation promoting factor (MPF) and the mitogen-activated protein kinase (MAPK) cascade play critical roles in modulating oocyte meiotic cell-cycle progression. MPF is a critical heterodimer composed of CDK1 and cyclin B1. Activation of MPF and ERK1/2 requires the activation of maternal and mRNAs translation, respectively.

[Function and molecular mechanism of mitogen-activated protein kinase (MAPK) in regulating oocyte meiotic maturation and ovulation].

The mitogen-activated protein kinase (MAPK) signaling pathway is a highly conserved signal transduction pathway from yeast to human species, and is widely distributed in various eukaryotic cells. In almost all of the species studied over the past three decades, this signaling pathway plays a crucial role in the development of female germ cells and meiotic maturation. Especially in a variety of mammalian species including primates, rodents, and domestic animals, the MAPK signaling pathway is activated during the resumption of first oocyte meiosis and plays an indispensable role in meiotic spindle assembly and cell cycle progression.

CFP1-dependent histone H3K4 trimethylation in murine oocytes facilitates ovarian follicle recruitment and ovulation in a cell-nonautonomous manner.

CxxC-finger protein 1 (CFP1)-mediated trimethylated histone H3 at lysine-4 (H3K4me3) during oocyte development enables the oocyte genome to establish the competence to generate a new organism. Nevertheless, it remains unclear to which extent this epigenetic modification forms an instructive component of ovarian follicle development. We investigated the ovarian functions using an oocyte-specific Cxxc1 knockout mouse model, in which the H3K4me3 accumulation is downregulated in oocytes of developing follicles.

A combinatorial code for mRNA 3'-UTR-mediated translational control in the mouse oocyte.

Meiotic maturation of mammalian oocytes depends on the temporally and spatially regulated cytoplasmic polyadenylation and translational activation of maternal mRNAs. Cytoplasmic polyadenylation is controlled by cis-elements in the 3'-UTRs of mRNAs including the polyadenylation signal (PAS), which is bound by the cleavage and polyadenylation specificity factor (CPSF) and the cytoplasmic polyadenylation element (CPE), which recruits CPE binding proteins. Using the 3'-UTRs of mouse Cpeb1, Btg4 and Cnot6l mRNAs, we deciphered the combinatorial code that controls developmental stage-specific translation during meiotic maturation: (i) translation of a maternal transcript at the germinal vesicle (GV) stage requires one or more PASs that locate far away from CPEs; (ii) PASs distal and proximal to the 3'-end of the transcripts are equally effective in mediating translation at the GV stage, as long as they are not close to the CPEs; (iii) Both translational repression at the GV stage and activation after germinal vesicle breakdown require at least one CPE adjacent to the PAS; (iv) The numbers and positions of CPEs in relation to PASs within the 3'-UTR of a given transcript determines its repression efficiency in GV oocytes.

CFP1 coordinates histone H3 lysine-4 trimethylation and meiotic cell cycle progression in mouse oocytes.

Trimethylation of histone H3 on lysine-4 (H3K4me3) is associated with gene-regulatory elements, but its transcription-independent function in cell division is unclear. CxxC-finger protein-1 (CFP1) is a major mediator of H3K4 trimethylation in mouse oocytes. Here we report that oocyte-specific knockout of Cxxc1, inhibition of CFP1 function, or abrogation of H3K4 methylation in oocytes each causes a delay of meiotic resumption as well as metaphase I arrest owing to defective spindle assembly and chromosome misalignment.