Gene Expression
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Career History:2008- present: Professor, Dept of Molecular Biology and Biotechnology, |
The transport of mRNA from the nucleus to the cytoplasm in human cellsIn eukaryotes mRNA is produced in the nucleus through the process of transcription but then has to be transported to the cytoplasm where it is translated to generate proteins in the cell. We study how mRNA is exported from the nucleus to the cytoplasm mainly in human cells and how this process is coupled with transcription and RNA processing events such as splicing, capping and polyadenylation. We use a wide variety of techniques to study this process including X-ray crystallography, NMR, microscopy, molecular biology and biochemistry. The images below show some results using microscopy techniques to look at where mRNA export factors are found in the cell. They also show what happens to mRNA when we deplete these factors using RNA interference techniques. |
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 FIGURE 1 : A) SPLICING FACTORS AND mRNA EXPORT FACTORS COLOCALISE IN NUCLEAR SPECKLES IN HUMAN CELLS. A GFP-fusion of the Tap mRNA export factor colocalises with the nuclear pore (signal around the rim of the nucleus) and the nuclear speckles. Tap colocalises in the nuclear speckles with the splicing factor SC35. |
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 FIGURE 1 : B) DEPLETION OF TAP USING RNAi BLOCKS mRNA EXPORT. RNA interference in human cells demonstrates that Tap is essential for mRNA export from the nucleus. YFP-tubulin is used as a transfection marker to highlight those cells which have been transfected with an RNA interference vector which causes depletion of Tap protein. The central panel shows the distribution of mRNA, detected using fluorescence in situ hybridisation with labelled oligodT which hybridises to the polyA tails on mRNA. |
Recent Publications |
| Teng, I and Wilson, S.A. (2013) Mapping Interactions between mRNA export factors in living cells. PLOS ONE, In press |
| Chang, C-T., Hautbergue, G.M., Walsh, M.J., Viphakone, N., van Dijk, T.B., Philipsen, S. and Wilson, S.A. (2013). Chtop is a component of the dynamic TREX mRNA export complex. EMBO J. 32:473-486 |
| Viphakone, N., Hautbergue, G.M., Walsh, M., Chang, C-T., Holland, A., Folco, E.G., Reed, R. & Wilson, S.A. (2012). TREX exposes the RNA binding domain of Nxf1 to enable mRNA export. Nature Communications, 3:1006 |
| Hautbergue, G.M. and Wilson, S.A. (2012) BLF1, the first Burkholderia pseudomallei toxin connects inhibition of host protein synthesis with melioidosis. Biochem. Soc. Trans. 40:842-845 |
| Knuckles, P., Vogt, M., Lugert, S., Milo, M., Chong, M.M., Hautbergue, G.M., Wilson, S.A., Littmann, D. and Taylor, V. (2012). Drosha regulates neurogenesis by controlling Neurogenin2 expression independent of microRNAs. Nature Neuroscience, 15:962-969 |
| Phelan, M.M., Goult, B.T., Clayton, J.C., Hautbergue, G.M., Wilson, S.A. and Lian, L-Y. (2011) The structure and selectivity of SR protein SRSF2 RRM domain with RNA. Nucleic Acids Res. 40:3232-3244 |
| Cruz-Migoni, A.*, Hautbergue,G.M. *, Artymiuk, P., Baker, P.J., Bokori-Brown, M., Chang, C.T., Dickman, M., Essex-Lopresti, A., Harding, S.V., Mahadi, N., Marshall, L.E., Mohamed, R., Nathan, S., Ngugi, S.A., Ong, C., Ooi, W.F., Partridge, L.J., Raih, F., Ruzhenikov, S., Sakar-Tyson, M., Sedelnikova,S.E., Smither,S.J., Tan, P., Titball, R.W., Wilson,S.A. #, Rice, D.W. # (2011) A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A. * joint first authors; # joint corresponding authors Science 324:821-824 |
| Jackson, B.R., Boyne, J.R., Noerenberg, M., Taylor, A., Hautbergue, G., Walsh, M.J., Wilson, S.A. and Whitehouse, A. (2011) An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export Plos Pathogens 7:e100213 |
| Van Hateren, N.J., Das, R.M., Hautbergue, G., Borycki, A.G., Placzek, M. and Wilson, S.A. (2011) FatJ acts via the Hippo mediator Yap1 to restrict the size of neural progenitor cell pools. Development 138:1893-1902 |
| Tunnicliffe, R.B., Hautbergue, G.M. Kalra, P., Jackson, B.R., Whitehouse, A., Wilson, S.A. and Golovanov, A.P. (2011) Structural basis for the recognition of cellular mRNA export factor REF by herpes viral proteins SV-1 ICP27 and HVS ORF57. PLOS Pathogens 7(1): e1001244 |
| Clayton, J.C., Phelan, M., Goult, B.T., Hautbergue,G.M., Wilson, S.A. and Lian, L.Y. (2011) The 1H, 13C and 15N backbone and side-chain assignment of the RRM domain of SC35, a regulator of pre-mRNA splicing. Biomol NMR assign 5:7-10 |
Selected earlier publications: |
| Dufu, K., Livingstone, M.J., Seebacher, J., Gygi, S.P., Wilson, S.A. and Reed, R. (2010) ATP is required for interactions between UAP56 and two conserved mRNA export proteins ALY and CIP29 to assemble the TREX complex. Genes and Development 24:2043-53 |
| Hautbergue, G.M., Hung, M.L., Walsh, M.J., Jones, R., Snijders, A.P., Dickman, M.J. and Wilson, S.A. (2009). UIF, a New mRNA Export Adaptor Which Works Together with REF/ALY, Requires FACT for Recruitment to mRNA. Current Biology 19:1918-1924 |
| Hautbergue, G.M., Hung, M.L., Golovanov, A.P. Lian, L.Y., and Wilson, S.A. (2008) Mutually exclusive interactions drive hand over of mRNA from export adaptors to TAP PNAS 105:5154-5159 |
| Shiau, C.E., Lwigale, P.Y., Das, R.M, Wilson, S.A., Bronner-Fraser, M. (2008) Robo2/Slit1 dependent cell-cell interactions mediate assembly of the trigeminal ganglion. Nature Neuroscience 11:269-276 |
| Manning, E., Ohyama, K., Saeger, B.,Hatano, O., Wilson, S.A., Logan, M. and Placzek, M. (2006) Regional morphogenesis in the Hypothalamus: A BMP-Tbx2 pathway co-ordinates fate and proliferation through Shh downregulation. Developmental Cell 11:873-885 |
| Hargous, Y.*, Hautbergue, G.*, Tintaru, A.M.*, Skrisovska, L., Golovanov, A., Stevenin, J., Lian, L-Y., Wilson, S.A.** and Allain, F.H.** (2006) Molecular basis of RNA recognition and TAP binding by the SR proteins SRp20 and 9G8. EMBO J. 25:5126-5137 *joint first authors; **corresponding authors |
| Hubbard, S.J., Grafham, D.V., Beattie, K.J., Overton, I.M., McLaren, S.R., Croning, M.D.R., Boardman, P.E., Bonfield, J.K., Burnside, J., Davies, R.M. Farrell, E.R., Francis, M.D., Griffiths-Jones, S. Humphray, S.J.,Hyland, C., Scott, C.E., Tang, H., Taylor, R.G., Tickle, C., Brown, W.R.A., Birney, E., Rogers, J. and Wilson. S.A. (2005). Transcriptome Analysis for the Chicken Based on 19,626 Finished cDNA Sequences and 485,337 Expressed Sequence Tags. Genome Research 15:174-183 |
| Wong, G.K et al. (2004) A polymorphism map for chicken with 2.8 million single nucleotide polymorphisms. Nature 432:717-722 |
| Hillier, L.W. et al. (2004) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432:695-716 |
| Brown, W.R.A., Hubbard, S.J., Tickle, C. and Wilson, S.A. (2003) The chicken as a model for large-scale analysis of vertebrate gene function. Nature Reviews Genetics 4: 87-98 |
| Boardman, P., Sanz-Ezquerro, J., Overton, I., Burt, D., Bosch, E., Fong, W.,Tickle, C., Brown, W.R.A., Wilson, S.A. and Hubbard, S.J. (2002) A comprehensive collection of chicken cDNAs. Current Biology 12: 1965-1969 |
| Koffa, M.D., Clements, J.B., Izaurralde, E., Wadd, S., Wilson, S.A., Mattaj, I.W. and Kuersten, S. (2001) Herpes simplex virus ICP27 protein provides viral mRNAs with access to the cellular mRNA export pathway. EMBO J. 20: 5769-5778 |
| Wilson, S.A., Wachira, S.M., Norton, R., Pearl, L.H. and Drew, R.E. (1996) Transcription antitermination regulation of the Pseudomonas aeruginosa amidase operon. EMBO J. 15: 5907-5916 |
| Pearl, L.H., O’Hara, B., Drew, R.E. and Wilson, S.A. (1994) Crystal structure of AmiC: the controller of transcription antitermination in the amidase operon of Pseudomonas aeruginosa. EMBO J. 13: 5810-5817 |
| Wilson, S.A., Wachira, S.M., Drew, R.E., Jones, D.T. and Pearl, L.H. (1993) Antitermination of amidase expression in Pseudomonas aeruginosa is controlled by a novel cytoplasmic amide-binding protein. EMBO J. 12: 3637-3642 |
Prof S A Wilson