We are interested in understanding the roles of Drosophila RNA-binding proteins in the regulation of gene expression during development. The proteins we study have a common RNA-binding domain (the RNA recognition motif or RRM) that has been found in many proteins involved in mRNA metabolism. We use a variety of approaches, including molecular biology, biochemistry and genetics, to assess the functions of these proteins and to identify the RNAs and other proteins with which they interact.
Currently, our studies are focussed on the TSR, RB97D and CAZ proteins. TSR and RB97D are required for normal male fertility. RB97D is a nuclear protein that is associated with RNAs from one of the lampbrush loops that forms on the heterochromatic Y chromosome during spermatogenesis. The phenotype of mutations in RB97D is similar to the effects of loss of that loop, consistent with the idea that RB97D has a role in processing loop transcripts. In contrast, TSR is a cytoplasmic protein whose expression pattern suggests involvement in translational regulation during spermatogenesis. Studies of CAZ have shown that it is a nuclear proteins whose expression is widespread but not ubiquitous during development. It is homologous to several human proteins (EWS and TLS) that are involved in translocations leading to sarcoma formation. A genetic analysis is underway to assess the in vivo function of CAZ.
Haynes, S.R., Cooper, M.T., Pype, S. and Stolow, D.T.: Involvement of a tissue-specific RNA Recognition Motif protein in Drosophila spermatogenesis. Molec. Cell. Biol. 17(May): 1997.
Heatwole, V.M. and Haynes, S.R.: Association of RB97D, an RRM protein required for male fertility, with a Y chromosome lampbrush loop in Drosophila spermatocytes. Chromosoma, 105:285-292, 1996.
Zu, K., Sikes, M.L., Haynes, S.R., and Beyer, A.L.: Altered levels of the Drosophila HRB87F/hrp36 hnRNP protein have limited effects on alternative splicing in vivo. Molec. Biol. Cell, 7:1059-1073, 1996.
Haynes, S.R.: Posttranscriptional regulation and RNA binding proteins in development. J. Biomed. Sci., 2: 293-301, 1995.
Stolow, D.T., and Haynes, S.R. (1995) Cabeza, a Drosophila gene encoding a novel RNA binding protein, shares homology with EWS and TLS, two genes involved in human sarcoma formation. Nucleic Acids Res., 23:835-843.