Cytoplasmic polyadenylation in mammalian oocyte maturation

Cytoplasmic polyadenylation element binding protein (CPEB) model of cytoplasmic polyadenylation (CP) and translational regulation in Xenopus. CPEB is the central protein (in yellow) that interacts with other key factors (in blue), such as Pumilio (PUM) and cleavage and polyadenylation specificity factor (CPSF), which together modulate formation of intricate protein complexes (in pink) responsible for repressing (red line) mRNA (brown line) translation in germinal vesicle and subsequently promoting CP and translational activation (green line) in metaphase II oocytes. A heterotrimer of two CPEB and one Maskin protein induce loop formation between the RNA termini as Maskin binds eukaryotic initiation factor 4E (eIF4E) preventing interaction between eIF4E and eukaryotic initiation factor 4G (eIF4G), precluding translation initiation. Symplekin (SYMPK) is believed to be a scaffolding protein enhancing CPSF and CPEB interaction prior to and during CP. In addition, CPEB interacts with a poly(A) polymerase, PAP associated domain containing 4 (PAPD4, aka GLD2), and poly(A)‐specific ribonuclease (PARN) which additionally interact with each other. Prior to translational activation PARN mediates deadenylation of transcripts, which is subsequently ejected from the complex upon CPEB phosphorylation (green circle) enabling CP. CPEB phosphorylation also results in its dissociation from embryonic poly(A) binding protein (ePAB, PABPC1L) which can then bind the newly synthesized poly(A) tail along with eIF4G displacing Maskin and enabling translational activation by mediating interaction of the eIF4 factors. Although PUM is not necessary for CPEB‐mediated translational regulation it has been found to enhance repression and translational activation under different contexts by interacting with CPEB, but has also been shown to induce repression independently of CPEB by recruitment of deadenylases (CCR4/NOT complex) and competing with eIF4E for 5′ end cap (black circle) binding which may extend to the CPEB model.

3′ untranslated region (UTR) motif analysis of the CCNB1 and MOS genes for human, mouse, and cattle. Horizontal bars (gray) represent 3′UTR sequence only from the last exon measured in base pairs (bp), which for human includes two annotated mRNA splice variants (horizontal black lines). Cytoplasmic polyadenylation element (CPE) consensus (CPE‐C), CPE nonconsensus (CPE‐NC), CPE mammalian MOS (CPE‐MamMOS); hexanucleotide polyadenylation signal (Hex), Musashi binding element (MBE), Pumilio binding element (PBE), and translational control sequence (TCS).

Expression of polyadenylation and translational regulator associated factors in mammalian metaphase II (MII) oocytes. Average gene expression values (RPKM) in human, mouse, and cattle MII oocytes. Genes failing to meet the expression cutoff (RPKM > 0.4 in at least two oocyte samples from their respective species) were assigned an RPKM ≤ 0.4 and are not considered to be expressed (red). Red and green represent the lowest and highest expression, respectively, across species and between genes belonging to respective gene families (CPEB, CPSF, DAZAP, MSI, PABP, PUM, and ZAR) or solely across species for respective genes not belonging to a gene family (DAZL, PAPD4, PARN, SYMPK, and TACC3).