Ozturk S (2019), The translational functions of embryonic poly(A...

XB-ART-56197

Mol Reprod Dev 2019 Nov 01;8611:1548-1560. doi: 10.1002/mrd.23253.

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The translational functions of embryonic poly(A)-binding protein during gametogenesis and early embryo development.

Ozturk S .

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Embryonic poly(A)-binding protein (EPAB) is an RNA-binding protein that binds to the poly(A) tails and AU-rich element at the 3' ends of messenger RNA (mRNAs). The main functions of EPAB are to protect stored mRNAs from undergoing deadenylation and subsequent degradation and to be involved in their translational regulation during spermatogenesis, oogenesis, and early embryogenesis. Following the first characterization of Epab in the Xenopus oocytes and early embryos, spatial and temporal expression and potential roles of the Epab gene have been determined in the vertebrate germ cells and early embryos. In this review, we have comprehensively evaluated all studies in this field and discussed the particular functions of EPAB in the spermatogenic cells, oocytes, early embryos, and somatic cells in vertebrates.

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Species referenced: Xenopus laevis
Genes referenced: cpeb1 dazl eif4b eif4e pabpc1 pabpc1l pabpc4 paip1 parn pum1 pum2 tacc3 tent2
GO keywords: spermatogenesis

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	Figure 1. The structure of embryonic poly(A)‐binding protein (EPAB) in Xenopus, mice and humans. The Epab mRNA is composed of 14 exons, and each exon contributes to encoding the EPAB domains. Basically, EPAB consists of four RNA recognition motifs (RRMs), proline‐rich linker region (PrLR) and poly(A)‐binding protein C‐terminal domain (PABC) domains. Each domain enables the binding of different sequences and/or factors to accomplish their specific missions. aa, amino acid; ARE, AU‐rich element; eRF3, eukaryotic release factor 3; Exs, exons; eIF4B and 4G, eukaryotic initiation factor 4B and 4G; PABPC1, poly(A)‐binding protein cytoplasmic 1; PAIP1, PABP‐interacting protein 1; miRNA, microRNA [Color figure can be viewed at wileyonlinelibrary.com]
	Figure 2. Translation control of cytoplasmic polyadenylation element (CPE)‐containing mRNAs and ringo/spy mRNA in Xenopus. (a) Translation of the repressed CPE‐containing mRNAs having short poly(A) tail takes place following phosphorylation of Cpeb1 by Aurora kinase. The Cpeb1 phosphorylation results in removing Maskin from the complex so that translation of the target mRNAs with long poly(A) tails bound by Epab appeares during oocyte maturation and early embryogenesis. (b) Upon oocyte maturation, the ringo/spy mRNA translation is carried out after removing Pum2 from the repression complex. Thus, the translation complex including Dazl‐Epab‐Eif4g‐Eif4e provides the ringo/spy mRNA translation independent of polyadenylation. AAAAAA, poly(A) tail; A, adenosine; AAUAAA, cleavage and polyadenylation signal; Cpeb1, cytoplasmic polyadenylation element binding protein 1; Cpsf, cleavage and polyadenylation specificity factor; Eif4e and 4g, eukaryotic initiation factor 4e and 4g; Epab, embryonic poly(A)‐binding protein; Gld2, germ line development 2; p, phosphorylation; Parn, poly(A)‐specific ribonuclease; Sympk, symplekin; U, uracil [Color figure can be viewed at wileyonlinelibrary.com]
	Figure 3. The relative changes of embryonic poly(A)‐binding protein (EPAB) and poly(A)‐binding protein cytoplasmic 1 (PABPC1) expression at mRNA and protein levels, transcription and maternal mRNAs level in mouse oocytes and early embryos. The Epab and Pabpc1 genes exhibit similar and different expression distributions at these stages of early development. The transcriptional activity decreases from GV oocytes to MII oocytes and ceases at the MII oocytes upon meiotic resumption until embryonic genome activation (EGA) at the 2‐cell embryos in mice, in which time transcriptional activity rises. Maternal mRNAs are increasingly stored during transcription in the GV oocytes of growing follicles, and their levels begin to gradually decrease from MII oocytes to 2‐cell embryos due to undergoing degradation after being used in the translation of the required proteins. Since maternal mRNAs are transcribed and stored during early oogenesis, their levels gradually increase in GV oocytes and then decreases to 2‐cell embryos. GV, germinal vesicle; MII, metaphase II [Color figure can be viewed at wileyonlinelibrary.com]
	The relative changes of embryonic poly(A)‐binding protein (EPAB) and poly(A)‐binding protein cytoplasmic 1 (PABPC1) expression at mRNA and protein levels, transcription and stored mRNAs in the spermatogenic cells during spermatogenesis in mice. The Epab and Pabpc1 genes exhibit similar mRNA and protein expression in the spermatogenic cells except for spermatogonia. As is well known, paternal mRNAs are transcribed and stored during early spermatogenesis, and their levels gradually decrease after the time point where transcription is ceased at the mid‐spermiogenesis. Consistently, stored paternal mRNA levels progressively increase through round spermatids and decrease from round spermatids to sperm cells. E, elongating spermatids; ES, elongated spermatids; RS, round spermatids; SC, spermatocytes; SG, spermatogonia [Color figure can be viewed at wileyonlinelibrary.com]
	Figure 5. The particular functions of embryonic poly(A)‐binding protein (Epab) is summarized based on the findings from Xenopus. Epab play key roles in: i) Rapid inducer of G2‐M in oocytes (ringo)/Speedy (spy) mRNA translation, ii) translation of cytoplasmic polyadenylation element (CPE)‐containing mRNAs, and iii) mRNA stabilization and protection from deadenylation. It is important to note that certain molecules are shown for simplicity in this schematic diagram. 7mG, 7‐methyl guanosine; A, adenosine; Eif4e and 4g, eukaryotic initiation factor 4e and 4g; Dazl, deleted in azoospermia‐like; Parn, poly(A)‐specific ribonuclease; PBE, pumilio binding element [Color figure can be viewed at wileyonlinelibrary.com]