Gene Expression

Prof S A Wilson

Career History:

2008- present: Professor, Dept of Molecular Biology and Biotechnology,
University of Sheffield
2008: Reader, Dept of Molecular Biology and Biotechnology, University of
Sheffield
2003-2007: Senior Lecturer, Dept of Molecular Biology and
Biotechnology, University of Sheffield
1999-2003: Lecturer Dept. of Biomolecular Sciences, UMIST
1996-1999: Weir Junior Research Fellow, University College Oxford
1995-1999: Wellcome Trust Career Development Fellow, Biochemistry Dept,
Oxford University
1991-1995: Post-doctoral fellow, Biochemistry Department, University
College London
1987-1991: PhD student, Biochemistry Department, University College London
1984-1987: Degree in Cell and Molecular Biology, Biophysics Department,
King's College London

The transport of mRNA from the nucleus to the cytoplasm in human cells

In 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.

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.

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.

Selected Publications

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

Lambeth, L.S., Van Hateren, N.J., Wilson, S.A. and Nair, V. (2010) A direct comparison of strategies for combinatorial RNA interference. BMC Molecular Biology. 11:77

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

Hung, M.L., Hautbergue, G.M., Snijders, A.P., Dickman, M.J. and Wilson, S.A. (2010). Arginine methylation of REF/ALY promotes efficient handover of mRNA to TAP/NXF1. Nucleic Acids Res. 38:3351-3361

Walsh, M.P., Hautbergue, G.M. and Wilson, S.A. (2010) The structure and function of mRNA export adaptor proteins. Biochem Soc. Trans. 38:232-236

Snijders, A.P.L., Hung, M.L., Wilson, S.A., Dickman, M.J. (2010) Analysis of arginine and lysine methylation utilising peptide separations at neutral pH and electron transfer dissociation mass spectrometry. J. Am. Soc. Mass Spec. 21:88-96

Wright, D., Ferjentsik, Z., Ching, S.W., Qiu, X., Jiang, Y-J., Malapert, P., Pouquie, O., Van Hateren, N., Wilson, S.A., Franco, C., Gerhardt, H., Dale, J.K. and Maroto, M. (2009). Cyclic Nrarp mRNA expression is regulated by the somitic oscillator but Nrarp protein levels do not oscillate. Developmental Dynamics 238:3043-3055

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

Tang, C.W., Maya-mendoza, A., Martin, C., Zeng, K., Chen, K., Feret, D., Wilson, S.A., and Jackson, D.A. (2008) The integrity of a lamin B1-dependent nucleoskeleton is a fundamental determinant of RNA synthesis in human cells. J.Cell Sci. 121:1014-1024

Van Hateren, N.J., Jones, R.S. and Wilson, S.A. (2008) RNA Interference In Chicken Embryos. pp295-314 In Electroporation Editor: Nakamura H. Publisher: Springer, Japan.

Van Hateren, N.J., Das, R.M. and Wilson, S.A. (2008) RNA Interference In Chicken Embryos. pp183-204 In RNA Interference- Methods for plants and animals Editors Doran, T. and Helliwell, C. CAB International, U.K.

Tintaru, A.M., Hautbergue, G.M., Hounslow, A.M., Hung, M.L., Lian, L.Y., Craven, C.J., and Wilson, S.A. (2007) Structural and functional analysis of RNA and TAP binding to SF2/ASF EMBO Rep. 8:756-762

Tintaru, A.M., Hautbergue, G.M., Hounslow, A.M., Lian, L.Y., Wilson, S.A., Craven, C.J. (2007) Assignment of 1H, 13C, and 15N resonances for SF2 RNA recognition motif 2. J. Biomol NMR 38:193

Smith T.G., Van Hateren, N., Tickle, C. and Wilson, S.A. (2007) The expression of Fat-1 cadherin during chick limb development. Int. J. Dev. Biol. 51:173-176

Golovanov, A.P., Hautbergue, G.M., Wilson, S.A. and Lian, L-Y. (2006). Assignment of 1H, 13C, and 15N resonances for the REF2-I mRNA export factor. J. Biomol. NMR 36:supp 5 p41

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

Golovanov, A.P.**, Hautbergue, G.M., Tintaru, A.M., Lian, L.Y and Wilson, S.A.** (2006) The solution structure of REF2-I reveals interdomain interactions and regions involved in binding mRNA export factors and RNA. RNA 12:1933-1948 **corresponding authors

Das, R.M., Van Hateren, N.J., Howell, G.R., Farrell, E.R., Bangs, F., Porteous, V.C., Manning, E.M., McGrew, M.J., Ohyama, K., Sacco, M.A., Halley, P.A., Sang, H.M., Storey, K.G., Placzek, M., Tickle, C., Nair, V.K. and Wilson, S.A. (2006) A robust system for RNA interference in the chicken using a modified microRNA operon. Developmental Biology 294:554-563

Selected Earlier Publications

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