title: Human embryonic poly(A)-binding protein (EPAB) alternative splicing is differentially regulated in human oocytes and embryos.
abstract: Oocyte maturation is associated with suppression of transcriptional activity. Consequently, gene expression during oocyte maturation, fertilization and early embryo development, until zygotic genome activation (ZGA) is primarily regulated by translational activation of maternally derived mRNAs. Embryonic poly(A)-binding protein (EPAB) is the predominant poly(A)-binding protein in Xenopus, mouse and human oocytes and early embryos prior to ZGA. EPAB plays a key role in polyadenylation-dependent translational activation of mRNAs by stabilizing polyadenylated mRNAs and by stimulating their translation. Epab-knockout female mice are sterile, fail to generate mature oocytes and display impaired cumulus expansion and ovulation. Consistent with its role during gametogenesis and early embryo development, Xenopus and mouse Epab mRNA is expressed exclusively in oocytes and early embryos, and is undetectable following ZGA or in somatic tissues. Herein, we demonstrate that although EPAB is expressed in human somatic tissues, its transcripts largely consist of an alternatively spliced form lacking the first 58 bp of exon 8, which leads to the formation of a premature stop codon 6 amino acids downstream on exon 8, and omission of the functionally critical poly(A)-binding domain. Moreover, 8-cell and blastocyst stage human embryos also express only the alternatively spliced form of EPAB. On the other hand, the full-length form of EPAB mRNA is exclusively expressed in oocytes. In conclusion, in contrast with the transcriptional regulation in Xenopus and mouse, oocyte- and early embryo-specific expression of EPAB in human is regulated by a post-transcriptional mechanism.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 310 Cedar Street, LSOG 304B, New Haven, CT 06520-8063, USA.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Guzeloglu-Kayisli
authors.forename: Maria D
authors.initials: MD
authors.lastname: Lalioti
authors.forename: Elnur
authors.initials: E
authors.lastname: Babayev
authors.forename: Saioa
authors.initials: S
authors.lastname: Torrealday
authors.forename: Cengiz
authors.initials: C
authors.lastname: Karakaya
authors.forename: Emre
authors.initials: E
authors.lastname: Seli
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009865:Oocytes / Q000254:growth & development; D009866:Oogenesis / Q000235:genetics*; D010060:Ovulation; D011061:Poly A / Q000235:genetics; D039102:Poly(A)-Binding Proteins / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: C531188:PABPC1L protein, human; D039102:Poly(A)-Binding Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011061:Poly A
keywords: alternative splicing; embryo; embryonic poly(A)-binding protein; oocyte; translational control