My research group is studying pre mRNA splicing in the yeast Saccharomyces cerevisiae. Prp8p, a U5 snRNP protein that interacts directly with the pre mRNA in spliceosomes, has been a focus of our research over many years. Prp8p is unusually large (280 kD) and both its size and sequence are conserved from yeast to man, suggesting that it plays a critical role in splicing. We recently showed that mutations in the C-terminus of Prp8 that cause Retinitis pigmentosa in humans, cause a defect in U5 snRNP maturation and splicing in yeast.
This type of Retinitis pigmentosa may therefore be a consequence of a splicing defect. We are also investigating links between transcription and splicing. I am co-ordinator of an EU-funded STREP "RiboSys" to investigate the systems biology of RNA metabolism in yeast.
- Boon, K.L., Grainger, R.J., Ehsani, P., Barrass, J.D., Auchynnikava, T., Inglehearne, C. and Beggs, J.D. (2007). prp8 mutations that cause human retinitis pigmentosa lead to a U5 snRNP maturation defect in yeast. Nature Structural and Molecular Biology 14, 1077-83.
- Spiller, M.J., Reijns, M.A.M. and Beggs, J.D. (2007). Requirements for nuclear localization of Lsm2-8p and competition between nuclear and cytoplasmic Lsm complexes. Journal of Cell Science 120, 4310-20.
- Spiller, M.J., Boon, K.L., Reijns, M.A.M. and Beggs, J.D. (2007). Lsm2-8 complex is required for nuclear localization of U6 snRNA. Nucleic Acids Research 35, 923-929.
- Boon, K.L., Auchynnikava, T., Edwalds-Gilbert, G., Barrass, J.D., Droop, A.P., Dez, C. and Beggs, J.D. (2006). Yeast Spp382/Ntr1 mediates Prp43 function in post-spliceosomes. Molecular and Cellular Biology 26, 6016-6023.
- Boon, K.L., Norman, C., Grainger, R.J., Newman, A.J. and Beggs, J.D. (2006). Prp8p dissection reveals domain structure and protein interaction sites. RNA 12, 198-205.
- Grainger, R.J. and Beggs, J.D. (2005). Prp8 protein; at the heart of the spliceosome. RNA 11, 533-557.
- Verdone, L., Galardi, S., Page, D. and Beggs, J.D. (2004). Lsm proteins promote regeneration of pre-mRNA splicing activity. Current Biology 14(16), 1487-91.
- van Nues, R. and Beggs, J.D. (2001). Functional contacts with a range of splicing proteins suggest a central role for Brr2p in the dynamic control of the order of events in spliceosomes. Genetics 157(4), 1451-67.
- Tharun, S., He, W., Mayes, A.E., Lennertz, P., Beggs, J.D. and Parker, R. (2000). Yeast Sm-like proteins function in mRNA decay. Nature 404(6777), 515-8.
Key lab techniques: yeast in vitro splicing assays, quantitative PCR, chromatin immunoprecipitation, yeast intron micro-array, yeast two-hybrid screening, fluorescence microscopy with yeast.
Key lab reagents: yeast intron micro-array, Prp8p antisera, ChIp reagents for yeast.
Lab contact: Jean Beggs: firstname.lastname@example.org
RiboSys website: http://www.ribosys.org