Structure of Dazl based translation control complexes

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Human fertility depends upon the production of mature sperm and eggs, and defects in the control of gene expression during this process contribute to infertility, a problem affecting 12-15% of couples worldwide. Deletions on the Y chromosome in infertile men suggested a fertility factor at this location and subsequent mapping identified the Deleted in AZoospermia (DAZ) gene. Members of the DAZ gene family are required for fertility in species across evolution. Mouse Dazl, a member of the DAZ gene family, is an RNA binding protein. Dazl recognises specific sequences on certain messenger RNAs in developing germ cells and recruits protein cofactors in order to regulate how much protein is produced from that mRNA, dictating expression of that gene. We aim to determine the three-dimensional structure of the Dazl protein bound to RNA or the protein cofactors. This will allow us to visualise the components of this system and how they interact at very high resolution, demonstrating how they normally function in controlling gene expression.