We are trying to understand how mRNA polyadenylation occurs in male germ cells in the absence of the canonical AAUAAA polyadenylation signal. We discovered and characterized a variant form of the CstF-64 polyadenylation protein that is expressed at high levels in meiotic and postmeiotic germ cells, and in no other tissue except the brain. This new protein, called """"""""(CstF-64,"""""""" is the leading candidate to account for AAUAAA-independent polyadenylation in germ cells. Our overall laboratory hypothesis is that (1) the somatic CstF-64 gene (Cstf2) is on the X chromosome in mice and humans, (2) the X-chromosomal CstF-64 is inactivated during male meiosis, (3) since CstF-64 function is essential, an auxiliary CstF-64 gene must be expressed from an autosome, and (4) the auxiliary CstF-64 protein is responsible for AAUAAA-independent polyadenylation of mRNAs in male germ cells and is essential for spermatogenesis. In the previous grant period, we addressed items 1-3 of our hypothesis. The goals of this grant proposal are to address item 4. This Independent Scientist Award (K02) will assist me in accomplishing those goals. Specifically, I am seeking to receive salary support to release me from some or all of my teaching and administrative duties so that I can devote a greater portion of my time to research and career development. For the research portion, I will be able to spend more time in the laboratory myself, and to direct the research of my workers more effectively. For the career development portion, I will be able to attend national and international meetings, and spend short periods visiting laboratories of collaborators to learn new techniques relevant to our work. These activities will be especially helpful, because my background is in biochemistry and not in reproductive biology. The Department of Cell Biology & Biochemistry is an excellent place from which to achieve these goals: the major strength of the Department is in many aspects of reproductive biology, and my colleagues have been exceedingly generous in sharing their ideas and expertise. This environment, supplemented with trips to meetings and visits to collaborators, will provide excellent support for my endeavors.
| D'mello, Veera; Lee, Ju Y; MacDonald, Clinton C et al. (2006) Alternative mRNA polyadenylation can potentially affect detection of gene expression by affymetrix genechip arrays. Appl Bioinformatics 5:249-53 |
