Jean Beggs

Research Focus

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.

Publications

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. Grainger, R.J. and Beggs, J.D. (2005). Prp8 protein; at the heart of the spliceosome. RNA 11, 533-557.
  7. 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.
  8. 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.
  9. 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: j.beggs@ed.ac.uk

Lab website: www.homepages.ed.ac.uk/jeanb; http://www.wcb.ed.ac.uk/beggs

RiboSys website: http://www.ribosys.org