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)
- The tudor SND1 protein is an m6A RNA reader essential for replication of Kaposi’s sarcoma-associated herpesvirus. eLife, 8. View this article in WRRO
- Co-transcriptional Loading of RNA Export Factors Shapes the Human Transcriptome. Molecular Cell. View this article in WRRO
- The m6A‑methylase complex and mRNA export. Biochimica et Biophysica Acta - Gene Regulatory Mechanisms. View this article in WRRO
- The m6A-methylase complex recruits TREX and regulates mRNA export. Scientific Reports, 8(1). View this article in WRRO
- The role of TREX in gene expression and disease.. The Biochemical journal, 473(19), 2911-2935. View this article in WRRO
- 227 Luzp4 defines a new mRNA export pathway in cancer cells. European Urology Supplements, 14(2), e227-e227b.
- 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.
- 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
- Luzp4 defines a new mRNA export pathway in cancer cells. Nucleic Acids Research, 43(4), 2353-2366. View this article in WRRO
- 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
- Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansions.. Brain, 137(Pt 7), 2040-2051. View this article in WRRO
- 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
- Chtop is a component of the dynamic TREX mRNA export complex.. EMBO J, 32(3), 473-486.
- Erratum: TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export. Nature Communications, 4(1).
- Mapping interactions between mRNA export factors in living cells.. PLoS One, 8(6), e67676. View this article in WRRO
- TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export.. Nat Commun, 3, 1006. View this article in WRRO
- BLF1, the first Burkholderia pseudomallei toxin, connects inhibition of host protein synthesis with melioidosis.. Biochem Soc Trans, 40(4), 842-845.
- Drosha regulates neurogenesis by controlling neurogenin 2 expression independent of microRNAs.. Nat Neurosci, 15(7), 962-969.
- 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
- A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A.. Science, 334(6057), 821-824. View this article in WRRO
- 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
- FatJ acts via the Hippo mediator Yap1 to restrict the size of neural progenitor cell pools.. Development, 138(10), 1893-1902.
- 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
- 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.
- 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
- Structure and function of mRNA export adaptors.. Biochem Soc Trans, 38(Pt 1), 232-236.
- 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.
- A direct comparison of strategies for combinatorial RNA interference. BMC MOL BIOL, 11. View this article in WRRO
- 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.
- 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.
- Cyclic Nrarp mRNA Expression Is Regulated by the Somitic Oscillator but Nrarp Protein Levels Do Not Oscillate. DEV DYNAM, 238(12), 3043-3055.
- UIF, a New mRNA export adaptor that works together with REF/ALY, requires FACT for recruitment to mRNA.. Curr Biol, 19(22), 1918-1924.
- 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.
- Mutually exclusive interactions drive handover of mRNA from export adaptors to TAP.. Proc Natl Acad Sci U S A, 105(13), 5154-5159.
- Robo2-Slit1 dependent cell-cell interactions mediate assembly of the trigeminal ganglion. NAT NEUROSCI, 11(3), 269-276.
- Structural and functional analysis of RNA and TAP binding to SF2/ASF.. EMBO Rep, 8(8), 756-762.
- Assignment of 1H, 13C, and 15N resonances for SF2 RNA recognition motif 2.. J Biomol NMR, 38(2), 193.
- The expression of Fat-1 cadherin during chick limb development. INT J DEV BIOL, 51(2), 173-176.
- Regional morphogenesis in the hypothalamus: a BMP-Tbx2 pathway coordinates fate and proliferation through Shh downregulation.. Dev Cell, 11(6), 873-885.
- The solution structure of REF2-I reveals interdomain interactions and regions involved in binding mRNA export factors and RNA.. RNA, 12(11), 1933-1948.
- Molecular basis of RNA recognition and TAP binding by the SR proteins SRp20 and 9G8.. EMBO J, 25(21), 5126-5137.
- A robust system for RNA interference in the chicken using a modified microRNA operon.. Dev Biol, 294(2), 554-563.
- Assignment of 1H, 13C, and 15N resonances for the REF2-I mRNA export factor.. J Biomol NMR, 36 Suppl 1, 41.
- 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.
- Transcriptome analysis for the chicken based on 19,626 finished cDNA sequences and 485,337 expressed sequence tags. GENOME RES, 15(1), 174-183.
- Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. NATURE, 432(7018), 695-716.
- A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms. NATURE, 432(7018), 717-722.
- A simple method for improving protein solubility and long-term stability.. J Am Chem Soc, 126(29), 8933-8939.
- The chicken as a model for large-scale analysis of vertebrate gene function. NAT REV GENET, 4(2), 87-98.
- A comprehensive collection of chicken cDNAs.. Curr Biol, 12(22), 1965-1969.
- Epithelial membrane proteins induce membrane blebbing and interact with the P2X7 receptor C terminus.. J Biol Chem, 277(37), 34017-34023.
- Herpes simplex virus ICP27 protein provides viral mRNAs with access to the cellular mRNA export pathway. EMBO J, 20(20), 5769-5778.
- Characterization of the equine infectious anaemia virus S2 protein.. J Gen Virol, 81(Pt 9), 2189-2194.
- Structural adaptation to selective pressure for altered ligand specificity in the Pseudomonas aeruginosa amide receptor, amiC.. Protein Eng, 13(2), 129-132.
- 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.
- 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.
- 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.
- Oligomerization of the amide sensor protein AmiC by X-ray and neutron scattering and molecular modeling. Biochemistry, 36(26), 8020-8029.
- Structural determinants within the subunit protein of Ty1 virus‐like particles. Molecular Microbiology, 22(4), 667-679.
- Transcription antitermination regulation of the Pseudomonas aeruginosa amidase operon. EMBO Journal, 15(21), 5907-5916.
- 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.
- Transcriptional analysis of the amidase operon from Pseudomonas aeruginosa.. Journal of bacteriology, 177(11), 3052-3057.
- Crystal structure of AmiC: the controller of transcription antitermination in the amidase operon of Pseudomonas aeruginosa.. The EMBO Journal, 13(24), 5810-5817.
- Antitermination of amidase expression in Pseudomonas aeruginosa is controlled by a novel cytoplasmic amide-binding protein.. The EMBO Journal, 12(9), 3637-3642.
- 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.
- 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.
- RNA Interference in Chicken Embryos In Nakamura H (Ed.), Electroporation and Sonoporation in Developmental Biology (pp. 295-314). Springer Verlag
- 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
- 13-P051 A temporal integration of BMP signalling controls progressive progenitor specification in the ventral diencephalon. Mechanisms of Development, Vol. 126 (pp S210-S210)