MicroRNA-196a regulates bovine newborn ovary homeobox gene (NOBOX) expression during early embryogenesis

BMC Developmental Biology

Jianbo Yao²  George W Smith¹  Gabbine Wee³  Kyung-Bon Lee³  Swamy K Tripurani² 

[1] Department of Physiology, Michigan State University, East Lansing, MI 48824, USA;Laboratory of Animal Biotechnology and Genomics, Division of Animal and Nutritional Sciences, West Virginia University, Morgantown, WV 26506, USA;Laboratory of Mammalian Reproductive Biology and Genomics, Department of Animal Science, Michigan State University, East Lansing, MI 48824, USA

关键词: maternal to zygotic transition;    microRNA;    early embryogenesis;    oocyte;    bovine;    NOBOX;   

Others  :  1126136
DOI  :  10.1186/1471-213X-11-25

 received in 2011-01-24, accepted in 2011-05-06,  发布年份 2011

【 摘 要 】

Background

Oocyte-derived maternal RNAs drive early embryogenesis when the newly formed embryo is transcriptionally inactive. Recent studies in zebrafish have identified the role of microRNAs during the maternal-to-embryonic transition (MET). MicroRNAs are short RNAs that bind to the 3' UTR of target mRNAs to repress their translation and accelerate their decay. Newborn ovary homeobox gene (NOBOX) is a transcription factor that is preferentially expressed in oocytes and essential for folliculogenesis in mice. NOBOX knockout mice are infertile and lack of NOBOX disrupts expression of many germ-cell specific genes and microRNAs. We recently reported the cloning and expression of bovine NOBOX during early embryonic development and our gene knockdown studies indicate that NOBOX is a maternal effect gene essential for early embryonic development. As NOBOX is a maternal transcript critical for development and NOBOX is depleted during early embryogenesis, we hypothesized that NOBOX is targeted by microRNAs for silencing and/or degradation.

Results

Using an algorithm "MicroInspector", a potential microRNA recognition element (MRE) for miR-196a was identified in the 3' UTR of the bovine NOBOX mRNA. Expression analysis of miR-196a in bovine oocytes and during early embryonic development indicated that it is expressed both in oocytes and embryos and tends to increase at the four-cell and eight-cell stages. Ectopic expression of NOBOX and miR-196a in HeLa cells inhibited the expression of NOBOX protein compared to the control cells without miR-196a. Similarly, the activity of a luciferase construct containing the entire 3' UTR of bovine NOBOX was suppressed, and the regulation was abolished by mutations in the miR-196a binding site indicating that the predicted MRE is critical for the direct and specific binding of miR-196a to the NOBOX mRNA. Furthermore, ectopic expression of miR-196a mimic in bovine early embryos significantly reduced the NOBOX expression at the both mRNA and protein levels.

Conclusion

Collectively, our results demonstrate that miR-196a is a bona fide negative regulator of NOBOX during bovine early embryogenesis.

【 授权许可】

   
2011 Tripurani et al; licensee BioMed Central Ltd.

【 图 表 】

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