Professor Stuart Wilson
Roper Chair in Genetics
Tel: 0114 222 2849
Professor Wilson’s laboratory studies how messenger RNA is transported from the nucleus to the cytoplasm in human cells. The group have a particularly interested in how this process is coupled with earlier mRNA processing events in the nucleus such as splicing, polyadenylation and RNA modifications such as methylation. They use a multidisciplinary approach to study this essential step in the gene expression pathway, combining molecular and cell biology techniques with the latest genome wide bioinformatic approaches. Current research areas include analysing how nuclear long non-coding RNAs and unprocessed mRNAs are kept in the nucleus and how this goes wrong in motor neuron disease associated with the C9ORF72 gene. Professor Wilson’s group are also analysing how DNA damage regulates mRNA export and how mRNA is packaged by the cell to help prevent the formation of R-loops which can trigger DNA damage.
Figure 1: 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.
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 2: 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.
Nucleic acids, mRNA export, RNA interference
Level 3 Modules
MBB325 The RNA World (Module Coordinator)
- Viphakone N, Sudbery I, Griffith L, Heath CG, Sims D & Wilson SA (2019) Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome. Molecular Cell.
- Lesbirel S & Wilson SA (2018) The m6A‑methylase complex and mRNA export. Biochimica et Biophysica Acta - Gene Regulatory Mechanisms. View this article in WRRO
- Lesbirel S, Viphakone N, Parker M, Parker J, Heath C, Sudbery I & Wilson SA (2018) The m6A-methylase complex recruits TREX and regulates mRNA export. Scientific Reports, 8(1). View this article in WRRO
- Heath CG, Viphakone N & Wilson SA (2016) The role of TREX in gene expression and disease.. The Biochemical journal, 473(19), 2911-2935. View this article in WRRO
- Cumberbatch MGK, Viphakone N, Livingstone M, Heath PR, Dickman M, Catto JWF & Wilson SA (2015) 227 Luzp4 defines a new mRNA export pathway in cancer cells. European Urology Supplements, 14(2), e227-e227b.
- Pang KH, Cumberbatch MG, Wilson SA & Catto JWF (2015) 527 N6-methyladenosine mRNA methylation in common human cancers: Identifying a potential role in androgen-resistance within prostate cancer. European Urology Supplements, 14(2), e527-e527a.
- Snijders AP, Hautbergue GM, Bloom A, Williamson JC, Minshull TC, Phillips HL, Mihaylov SR, Gjerde DT, Hornby DP, Wilson SA , Hurd PJ et al (2015) Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA. RNA, 21(3), 347-359. View this article in WRRO
- Viphakone N, Cumberbatch MG, Livingstone MJ, Heath PR, Dickman MJ, Catto JW & Wilson SA (2015) Luzp4 defines a new mRNA export pathway in cancer cells. Nucleic Acids Research, 43(4), 2353-2366. View this article in WRRO
- Caballero-Lima D, Hautbergue GM, Wilson SA & Sudbery PE (2014) In C andida albicans hyphae, Sec2p is physically associated with SEC2 mRNA on secretory vesicles. Molecular Microbiology, 94(4), 828-842. View this article in WRRO
- Cooper-Knock J, Walsh MJ, Higginbottom A, Robin Highley J, Dickman MJ, Edbauer D, Ince PG, Wharton SB, Wilson SA, Kirby J , Hautbergue GM et al (2014) Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansions.. Brain, 137(Pt 7), 2040-2051. View this article in WRRO
- Tunnicliffe RB, Hautbergue GM, Wilson SA, Kalra P & Golovanov AP (2014) Competitive and cooperative interactions mediate RNA transfer from herpesvirus saimiri ORF57 to the mammalian export adaptor ALYREF.. PLoS Pathog, 10(2), e1003907. View this article in WRRO
- Chang C-T, Hautbergue GM, Walsh MJ, Viphakone N, van Dijk TB, Philipsen S & Wilson SA (2013) Chtop is a component of the dynamic TREX mRNA export complex.. EMBO J, 32(3), 473-486.
- Viphakone N, Hautbergue GM, Walsh M, Chang C-T, Holland A, Folco EG, Reed R & Wilson SA (2013) Erratum: TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export. Nature Communications, 4(1), 2377.
- Teng I-F & Wilson SA (2013) Mapping interactions between mRNA export factors in living cells.. PLoS One, 8(6), e67676. View this article in WRRO
- Viphakone N, Hautbergue GM, Walsh M, Chang C-T, Holland A, Folco EG, Reed R & Wilson SA (2012) TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export.. Nat Commun, 3, 1006. View this article in WRRO
- Hautbergue GM & Wilson SA (2012) BLF1, the first Burkholderia pseudomallei toxin, connects inhibition of host protein synthesis with melioidosis.. Biochem Soc Trans, 40(4), 842-845.
- Knuckles P, Vogt MA, Lugert S, Milo M, Chong MMW, Hautbergue GM, Wilson SA, Littman DR & Taylor V (2012) Drosha regulates neurogenesis by controlling neurogenin 2 expression independent of microRNAs.. Nat Neurosci, 15(7), 962-969.
- Phelan MM, Goult BT, Clayton JC, Hautbergue GM, Wilson SA & Lian L-Y (2012) The structure and selectivity of the SR protein SRSF2 RRM domain with RNA.. Nucleic Acids Res, 40(7), 3232-3244. View this article in WRRO
- Cruz-Migoni A, Hautbergue GM, Artymiuk PJ, Baker PJ, Bokori-Brown M, Chang C-T, Dickman MJ, Essex-Lopresti A, Harding SV, Mahadi NM , Marshall LE et al (2011) A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A.. Science, 334(6057), 821-824.
- Jackson BR, Boyne JR, Noerenberg M, Taylor A, Hautbergue GM, Walsh MJ, Wheat R, Blackbourn DJ, Wilson SA & Whitehouse A (2011) An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export.. PLoS Pathog, 7(7), e1002138. View this article in WRRO
- Van Hateren NJ, Das RM, Hautbergue GM, Borycki A-G, Placzek M & Wilson SA (2011) FatJ acts via the Hippo mediator Yap1 to restrict the size of neural progenitor cell pools.. Development, 138(10), 1893-1902.
- Tunnicliffe RB, Hautbergue GM, Kalra P, Jackson BR, Whitehouse A, Wilson SA & Golovanov AP (2011) Structural basis for the recognition of cellular mRNA export factor REF by herpes viral proteins HSV-1 ICP27 and HVS ORF57.. PLoS Pathog, 7(1), e1001244. View this article in WRRO
- Clayton JC, Phelan M, Goult BT, Hautbergue GM, Wilson SA & 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(1), 7-10.
- Hung M-L, Hautbergue GM, Snijders APL, Dickman MJ & Wilson SA (2010) Arginine methylation of REF/ALY promotes efficient handover of mRNA to TAP/NXF1.. Nucleic Acids Res, 38(10), 3351-3361. View this article in WRRO
- Walsh MJ, Hautbergue GM & Wilson SA (2010) Structure and function of mRNA export adaptors.. Biochem Soc Trans, 38(Pt 1), 232-236.
- Lambeth LS, Van Hateren NJ, Wilson SA & Nair V (2010) A direct comparison of strategies for combinatorial RNA interference. BMC MOL BIOL, 11. View this article in WRRO
- Dufu K, Livingstone MJ, Seebacher J, Gygi SP, Wilson SA & 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(18), 2043-2053.
- Clayton JC, Phelan M, Goult BT, Hautbergue GM, Wilson SA & Lian L-Y (2010) The 1H, 13C and 15N backbone and side-chain assignment of the RRM domain of SC35, a regulator of pre-mRNA splicing. Biomolecular NMR Assignments, 1-4.
- Snijders APL, Hung M-L, Wilson SA & Dickman MJ (2010) Analysis of arginine and lysine methylation utilizing peptide separations at neutral pH and electron transfer dissociation mass spectrometry.. J Am Soc Mass Spectrom, 21(1), 88-96.
- Wright D, Ferjentsik Z, Chong SW, Qiu XH, Jiang YJ, Malapert P, Pourquie O, Van Hateren N, Wilson SA, Franco C , Gerhardt H et al (2009) Cyclic Nrarp mRNA Expression Is Regulated by the Somitic Oscillator but Nrarp Protein Levels Do Not Oscillate. DEV DYNAM, 238(12), 3043-3055.
- Hautbergue GM, Hung M-L, Walsh MJ, Snijders APL, Chang C-T, Jones R, Ponting CP, Dickman MJ & Wilson SA (2009) UIF, a New mRNA export adaptor that works together with REF/ALY, requires FACT for recruitment to mRNA.. Curr Biol, 19(22), 1918-1924.
- Tang CW, Maya-Mendoza A, Martin C, Zeng K, Chen SB, Feret D, Wilson SA & Jackson DA (2008) The integrity of a lamin-B1-dependent nucleoskeleton is a fundamental determinant of RNA synthesis in human cells. J CELL SCI, 121(7), 1014-1024.
- Hautbergue GM, Hung M-L, Golovanov AP, Lian L-Y & Wilson SA (2008) Mutually exclusive interactions drive handover of mRNA from export adaptors to TAP.. Proc Natl Acad Sci U S A, 105(13), 5154-5159.
- Shiau CE, Lwigale PY, Das RM, Wilson SA & Bronner-Fraser M (2008) Robo2-Slit1 dependent cell-cell interactions mediate assembly of the trigeminal ganglion. NAT NEUROSCI, 11(3), 269-276.
- Tintaru AM, Hautbergue GM, Hounslow AM, Hung M-L, Lian L-Y, Craven CJ & Wilson SA (2007) Structural and functional analysis of RNA and TAP binding to SF2/ASF.. EMBO Rep, 8(8), 756-762.
- Tintaru AM, Hautbergue GM, Hounslow AM, Lian L-Y, Wilson SA & Craven CJ (2007) Assignment of 1H, 13C, and 15N resonances for SF2 RNA recognition motif 2.. J Biomol NMR, 38(2), 193.
- Smith TG, Van Hateren N, Tickle C & Wilson SA (2007) The expression of Fat-1 cadherin during chick limb development. INT J DEV BIOL, 51(2), 173-176.
- Manning L, Ohyama K, Saeger B, Hatano O, Wilson SA, Logan M & Placzek M (2006) Regional morphogenesis in the hypothalamus: a BMP-Tbx2 pathway coordinates fate and proliferation through Shh downregulation.. Dev Cell, 11(6), 873-885.
- Hargous Y, Hautbergue GM, Tintaru AM, Skrisovska L, Golovanov AP, Stevenin J, Lian L-Y, Wilson SA & Allain FH-T (2006) Molecular basis of RNA recognition and TAP binding by the SR proteins SRp20 and 9G8.. EMBO J, 25(21), 5126-5137.
- Golovanov AP, Hautbergue GM, Tintaru AM, Lian L-Y & Wilson SA (2006) The solution structure of REF2-I reveals interdomain interactions and regions involved in binding mRNA export factors and RNA.. RNA, 12(11), 1933-1948.
- Das RM, Van Hateren NJ, Howell GR, Farrell ER, Bangs FK, Porteous VC, Manning EM, McGrew MJ, Ohyama K, Sacco MA , Halley PA et al (2006) A robust system for RNA interference in the chicken using a modified microRNA operon.. Dev Biol, 294(2), 554-563.
- Golovanov AP, Hautbergue GM, Wilson SA & Lian L-Y (2006) Assignment of 1H, 13C, and 15N resonances for the REF2-I mRNA export factor.. J Biomol NMR, 36 Suppl 1, 41.
- Williams BJL, Boyne JR, Goodwin DJ, Roaden L, Hautbergue GM, Wilson SA & Whitehouse A (2005) The prototype gamma-2 herpesvirus nucleocytoplasmic shuttling protein, ORF 57, transports viral RNA through the cellular mRNA export pathway.. Biochem J, 387(Pt 2), 295-308.
- Hubbard SJ, Grafham DV, Beattie KJ, Overton IM, McLaren SR, Croning MDR, Boardman PE, Bonfield JK, Burnside J, Davies RM , Farrell ER et al (2005) Transcriptome analysis for the chicken based on 19,626 finished cDNA sequences and 485,337 expressed sequence tags. GENOME RES, 15(1), 174-183.
- Wong GKS, Liu B, Wang J, Zhang Y, Yang X, Zhang ZJ, Meng QS, Zhou J, Li DW, Zhang JJ , Ni PX et al (2004) A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms. NATURE, 432(7018), 717-722.
- Hillier LW, Miller W, Birney E, Warren W, Hardison RC, Ponting CP, Bork P, Burt DW, Groenen MAM, Delany ME , Dodgson JB et al (2004) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. NATURE, 432(7018), 695-716.
- Golovanov AP, Hautbergue GM, Wilson SA & Lian L-Y (2004) A simple method for improving protein solubility and long-term stability.. J Am Chem Soc, 126(29), 8933-8939.
- Brown WRA, Hubbard SJ, Tickle C & Wilson SA (2003) The chicken as a model for large-scale analysis of vertebrate gene function. NAT REV GENET, 4(2), 87-98.
- Boardman PE, Sanz-Ezquerro J, Overton IM, Burt DW, Bosch E, Fong WT, Tickle C, Brown WRA, Wilson SA & Hubbard SJ (2002) A comprehensive collection of chicken cDNAs.. Curr Biol, 12(22), 1965-1969.
- Wilson HL, Wilson SA, Surprenant A & North RA (2002) Epithelial membrane proteins induce membrane blebbing and interact with the P2X7 receptor C terminus.. J Biol Chem, 277(37), 34017-34023.
- Koffa MD, Clements JB, Izaurralde E, Wadd S, Wilson SA, Mattaj IW & Kuersten S (2001) Herpes simplex virus ICP27 protein provides viral mRNAs with access to the cellular mRNA export pathway. EMBO J, 20(20), 5769-5778.
- Yoon S, Kingsman SM, Kingsman AJ, Wilson SA & Mitrophanous KA (2000) Characterization of the equine infectious anaemia virus S2 protein.. J Gen Virol, 81(Pt 9), 2189-2194.
- O'Hara BP, Wilson SA, Lee AW, Roe SM, Siligardi G, Drew RE & Pearl LH (2000) Structural adaptation to selective pressure for altered ligand specificity in the Pseudomonas aeruginosa amide receptor, amiC.. Protein Eng, 13(2), 129-132.
- WILSON SA, SIEIRO-VAZQUEZ C, EDWARDS NJ, IOURIN O, BYLES ED, KOTSOPOULOU E, ADAMSON CS, KINGSMAN SM, KINGSMAN AJ & MARTIN-RENDON E (1999) Cloning and characterization of hIF2, a human homologue of bacterial translation initiation factor 2, and its interaction with HIV-1 matrix. Biochemical Journal, 342(1), 97-103.
- Wilson SA, Sieiro-Vazquez C, Edwards NJ, Iourin O, Byles ED, Kotsopoulou E, Adamson CS, Kingsman SM, Kingsman AJ & Martin-Rendon E (1999) Cloning and characterization of hIF2, a human homologue of bacterial translation initiation factor 2, and its interaction with HIV-1 matrix.. Biochem J, 342 ( Pt 1), 97-103.
- Wilson SA, Brown EC, Kingsman AJ & Kingsman SM (1998) TRIP: a novel double stranded RNA binding protein which interacts with the leucine rich repeat of flightless I.. Nucleic Acids Res, 26(15), 3460-3467.
- Chamberlain D, O'Hara BP, Wilson SA, Pearl LH & Perkins SJ (1997) Oligomerization of the amide sensor protein AmiC by X-ray and neutron scattering and molecular modeling. Biochemistry, 36(26), 8020-8029.
- Martin‐Rendon E, Marfany G, Wilson S, Ferguson DJP, Kingsman SM & Kingsman AJ (1996) Structural determinants within the subunit protein of Ty1 virus‐like particles. Molecular Microbiology, 22(4), 667-679.
- Wilson SA, Wachira SJM, Norman RA, Pearl LH & Drew RE (1996) Transcription antitermination regulation of the Pseudomonas aeruginosa amidase operon. EMBO Journal, 15(21), 5907-5916.
- WILSON SA, WILLIAMS RJ, PEARL LH & DREW RE (1995) IDENTIFICATION OF 2 NEW GENES IN THE PSEUDOMONAS-AERUGINOSA AMIDASE OPERON, ENCODING AN ATPASE (AMIB) AND A PUTATIVE INTEGRAL MEMBRANE-PROTEIN (AMIS). J BIOL CHEM, 270(32), 18818-18824.
- Wilson SA & Drew RE (1995) Transcriptional analysis of the amidase operon from Pseudomonas aeruginosa.. Journal of Bacteriology, 177(11), 3052-3057.
- Pearl L, O'Hara B, Drew R & Wilson S (1994) Crystal structure of AmiC: the controller of transcription antitermination in the amidase operon of Pseudomonas aeruginosa.. The EMBO Journal, 13(24), 5810-5817.
- Wilson SA, Wachira SJ, Drew RE, Jones D & Pearl LH (1993) Antitermination of amidase expression in Pseudomonas aeruginosa is controlled by a novel cytoplasmic amide-binding protein.. The EMBO Journal, 12(9), 3637-3642.
- Wilson SA, Chayen NE, Hemmings AM, Drew RE & Pearl LH (1991) Crystallization of and preliminary X-ray data for the negative regulator (AmiC) of the amidase operon of Pseudomonas aeruginosa. Journal of Molecular Biology, 222(4), 869-871.
- Wilson S & Drew R (1991) Cloning and DNA sequence of amiC, a new gene regulating expression of the Pseudomonas aeruginosa aliphatic amidase, and purification of the amiC product.. Journal of Bacteriology, 173(16), 4914-4921.
- Wilson SA, Van Hateren NJ & jones RS (2009) RNA Interference in Chicken Embryos In Nakamura H (Ed.), Electroporation and Sonoporation in Developmental Biology (pp. 295-314). Springer Verlag
- Wilson SA, van hateren NJ & das RM (2009) RNAi in chicken embryos In Doran DT & Helliwell C (Ed.), RNA interference: methods for plants and animals (pp. 183-204). CABI Publishing
Conference proceedings papers
- Ohyama K, Wilson S, Briscoe J & Placzek M (2009) 13-P051 A temporal integration of BMP signalling controls progressive progenitor specification in the ventral diencephalon. Mechanisms of Development, Vol. 126 (pp s210)