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Mol. Hum. Reprod. Advance Access published online on May 20, 2008
Molecular Human Reproduction, 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
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

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 Seli1,2, Aylin Yaba1, Ozlem Guzeloglu-Kayisli1 and Maria D. Lalioti1

1Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520 USA

2 Correspondance: Emre Seli, Yale University School of Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, 300 George Street, Suite 770J, New Haven, CT, 06511. Fax: (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 pre-implantation 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, 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 five-fold increase in the expression of the c.Ex10del alternative splicing variant in animals carrying rs56574G/G in the exon 10 compared to rs56574C/C at the same locus. Our findings suggest that single nucleotide polymorphisms 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 March 4, 2008; accepted on May 7, 2008.


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O. Guzeloglu-Kayisli, S. Pauli, H. Demir, M. D. Lalioti, D. Sakkas, and E. Seli
Identification and characterization of human embryonic poly(A) binding protein (EPAB)
Mol. Hum. Reprod., October 1, 2008; 14(10): 581 - 588.
[Abstract] [Full Text] [PDF]


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