Department of Biochemistry and Molecular Biology
Monash University
ANZSCDB Plenary Presentation
Presentation Title
Using C. elegans as a model to understand post-transcriptional gene regulation during oogenesis
Abstract
In most organisms, many germ cell mRNAs are produced and stored in a translationally repressed state and are activated at specific times during oocyte and early stages of embryonic development. One of the mechanisms of translational regulation is to prevent the formation of cap-dependent translation initiation complexes where eIF4E-binding proteins inhibit the formation of eIF4E-eIF4G complexes, resulting in translationally repressed mRNAs. Some of these translationally repressed mRNAs are thought to be stored in large RNA-protein perinuclear cytoplasmic granules called germ granules. We are studying germ granule formation using the C. elegans model system and have discovered a link between an eIF4E-binding protein, germ granule formation and translational repression. We propose a model in which broad-scale cap-dependent translation inhibitors and are targeted to specific mRNAs via their interaction with individual RNA-binding proteins.
Biographical
Peter Boag obtained a PhD from Melbourne University in Molecular Parasitology. Peter has spent the last six years in the Blackwell lab at Harvard Medical School, Boston, USA where he studied mechanisms of gene regulation in the germline and early embryo of the model organism C.elegans. Peter is also an Honorary Research Fellow of the Faculty of Veterinary Science of the University of Melbourne (where in collaboration with Professor Robin Gasser they investigate the biology of parasitic nematodes of socio-economic importance).
The Boag lab is primarily interested in understanding how post transcriptional gene regulation influences development and cellular function. In a number of cell types, such as oocytes and neurons, many mRNAs are transcribed but are not immediately translated. Instead, these mRNAs are maintained in a translationally repressed state in predicted RNA-protein storage granules and only become translated upon specific cues. Some of the proteins involved in the storage of oocyte mRNAs are also present in Processing-bodies (P-bodies), recently identified cytoplasmic granules where many mRNA regulatory pathways are present, including decapping- and nonsense-mediated mRNA degradation and small RNA-mediated translational silencing (e.g. micro RNAs). The emerging similarities between germline storage granules and P-bodies suggests that the formation of RNA-protein granules is a conserved and important mechanism for maintaining cellular homeostasis. We are interested in elucidating the mechanisms governing the formation and function of germline mRNA storage granules and their requirement for fertility and embryonic viability.
Recent Publications
Hammell CM, Lubin I, Boag PR, Blackwell TK, Ambros V. (2009) nhl-2 Modulates microRNA activity in Caenorhabditis elegans. Cell. 2009 Mar 6;136(5):926-38.
Boag, P. R., Atalay, A., Robida, S., Reinke, V. and Blackwell, T. K. (2008). Protection of specific maternal messenger RNAs by the P body protein CGH-1 (Dhh1/RCK) during Caenorhabditis elegans oogenesis. J Cell Biol 182, 543-57.
Gartner, A., Boag, P. R. and Blackwell, T. K. (2008). Germline survival and apoptosis. WormBook, 1-20.
Walker, A. K., Boag, P. R. and Blackwell, T. K. (2007). Transcription reactivation steps stimulated by oocyte maturation in C. elegans. Dev Biol 304, 382-93.
Lehtinen, M. K., Yuan, Z., Boag, P. R., Yang, Y., Villen, J., Becker, E.B., DiBacco, S., de la Iglesia, N., Gygi, S., Blackwell, T. K. et al. (2006). A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell 125, 987-1001.
Boag, P. R., Nakamura, A. and Blackwell, T. K. (2005). A conserved RNA-protein complex component involved in physiological germline apoptosis regulation in C. elegans. Development 132, 4975-86.
Further Information
Dr Peter Boag's Profile
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