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Human Molecular Genetics Advance Access originally published online on November 8, 2005
Human Molecular Genetics 2005 14(24):3899-3909; doi:10.1093/hmg/ddi414
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Dazl binds in vivo to specific transcripts and can regulate the pre-meiotic translation of Mvh in germ cells

Nicola Reynolds1, Brian Collier1,2, Klio Maratou1,{dagger}, Victoria Bingham1, Robert M. Speed1, Mary Taggart1, Colin A. Semple1, Nicola K. Gray1,2 and Howard J. Cooke1,*

1MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK and 2School of Molecular and Clinical Medicine, 3rd Floor Outpatients Department, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK

* To whom correspondence should be addressed. Tel: +44 1314678427; Fax: +44 1314678456; Email: howard.cooke{at}hgu.mrc.ac.uk

Received September 23, 2005; Accepted November 2, 2005

Gametogenesis is a complex process subject to strict controls at both levels of transcription and translation. Members of a family of conserved RNA-binding proteins encoded by the DAZ genes are required for the translational regulation of gene expression essential for this process. Although loss of DAZ family genes is associated with infertility in several organisms including humans, the identity of the transcripts regulated in vivo is unknown. Using a combination of immunoprecipitation and microarray analysis, we have identified a number of mRNAs that are bound by the murine Dazl protein both in vivo and in vitro. Sequence analysis shows that these transcripts contain binding sites for Dazl, which have been conserved during evolution between human, rat and mouse. We have focussed on mouse vasa homologue (Mvh), a gene that is essential for male gametogenesis, and show that Dazl stimulates translation via the Mvh 3'-UTR. Finally, we show that germ cells of Dazl null mice contain reduced levels of Mvh protein, indicating that Dazl-mediated regulation of Mvh translation is crucial for mammalian spermatogenesis.

{dagger} Present address: Neural Plasticity Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.


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