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Mol. Hum. Reprod. Advance Access originally published online on May 20, 2008
Molecular Human Reproduction 2008 14(7):393-398; doi:10.1093/molehr/gan028
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
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Alternative splicing of the mouse embryonic poly(A) binding protein (Epab) mRNA is regulated by an exonic splicing enhancer: a model for post-transcriptional control of gene expression in the oocyte

Emre Seli1, Aylin Yaba, Ozlem Guzeloglu-Kayisli and Maria D. Lalioti

Yale University School of Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences,300 George Street, Suite 770J, New Haven, CT 06511, USA

1 Correspondence address. Fax: +1-203-785-7134; E-mail: emre.seli{at}yale.edu

Embryonic poly(A) binding protein (EPAB), expressed in oocytes and early embryos, binds and stabilizes maternal mRNAs, and mediates initiation of their translation. We identified an alternatively spliced form of Epab lacking exon 10 (c.Ex10del) and investigated the regulation of Epab mRNA alternative splicing as a model for alternative splicing in oocytes and early preimplantation embryos. Specifically, we evaluated the following mechanisms: imprinting; RNA editing and exonic splicing enhancers (ESEs). Sequence analysis led to the identification of two single nucleotide polymorphisms (SNPs): one was detected in exon 9 (rs55858A/G), and served as a marker for the parental origin of the alternatively spliced form, and the other was found in exon 10 (rs56574G/C), and co-segregated with the exon 9 SNP. We found that the presence of rs56574G in exon 10 led to the formation of an ESE, leading to efficient exclusion of exon 10. Real-time RT–PCR results revealed a 5-fold increase in the expression of the c.Ex10del alternative splicing variant in animals carrying rs56574G/G in exon 10 compared with rs56574C/C at the same locus. Our findings suggest that SNPs may alter the ratio between alternative splicing variants of oocyte-specific proteins. The role that these subtle differences play in determining individual reproductive outcome remains to be determined.

Key words: embryonic poly(A) binding protein/oocyte/alternative splicing/exonic splicing enhancer

Submitted on March 8, 2008; resubmitted on May 4, 2008; accepted on May 7, 2008.


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