Gene Regulation
Group Leader:
Prof Vicky Cowling
Precise and responsive gene regulation directs development, organ function and immune responses. Common oncogenic mutations result in deregulation of gene expression which can result in the acquisition of deleterious cellular behaviours and escape from growth control. We aim to understand how gene expression is regulated through the RNA cap, a potent structure formed on RNA polymerase II transcripts which impacts on transcription, RNA processing and translation.
We investigate how the RNA capping enzymes are regulated by cellular signalling pathways and how they impact on gene expression and cell function. We explore the therapeutic value of targeting the RNA capping methyltransferases, identifying oncogenic pathways which render cells sensitive to inhibition of these enzymes.
Lab Reports
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Recent Publications
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Lab Members
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Recent Publications
2025
Galloway A, Knop K, Gomez-Moreira C, Xavier V, Thomson S, Yoshikawa H, Suska O, Lukoszek R, Kaskar A, Lamond AI, MacVicar T, Cowling VH. CMTR1 directs mitochondrial dynamics during T cell activation through epitranscriptomic regulation of splice isoforms. Cell Rep. 2025;44(10):116412.
Hankinson J, Young D, Wignall-Fleming EB, Lukoszek R, Cowling VH, Randall R, Goodbourn S. The Cap-proximal secondary structures of the 5’UTRs of parainfluenza virus 5 mRNAs specify differential sensitivity to type I interferon and IFIT1. J Gen Virol. 2025;106(3).
Mills JG, Hepburn LA, Cowling VH. RNMT-dependent RNA cap methylation in health and disease. Biochem J. 2025(18).
Pearson LA, Petit AP, Mendoza-Martinez C, Bellany F, Lin D, Niven S, Swift R, Eadsforth T, Fyfe PK, Paul M, Postis V, Hu X, Cowling VH, Gray DW. Characterisation of RNA guanine-7 methyltransferase (RNMT) using a small molecule approach. Biochem J. 2025.
2024
Lukoszek R, Inesta-Vaquera F, Brett NJM, Liang S, Hepburn LA, Hughes DJ, Pirillo C, Roberts EW, Cowling VH. CK2 phosphorylation of CMTR1 promotes RNA cap formation and influenza virus infection. Cell Rep. 2024;43(7):114405.
Pearson L-A, Petit A-P, Mendoza-Martinez C, Bellany F, Lin D, Niven S, Swift R, Eadsforth T, Fyfe PK, Paul M, Postis V, Hu X, Cowling V, Gray DW. Characterisation of RNA guanine-7 methyltransferase (RNMT) using a small molecule approach. bioRxiv. 2024:2024.2010.2003.614057.
Xavier V, Martinelli S, Corbyn R, Pennie R, Rakovic K, Powley IR, Officer-Jones L, Ruscica V, Galloway A, Carlin LM, Cowling VH, Le Quesne J, Martinou JC, MacVicar T. Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Sci Alliance. 2024;7(11).
2023
Knop K, Gomez-Moreira C, Galloway A, Ditsova D, Cowling VH. RAM is upregulated during T cell activation and is required for RNA cap formation and gene expression. Discov Immunol. 2024;3(1):kyad021.
Liang S, Almohammed R, Cowling VH. The RNA cap methyltransferases RNMT and CMTR1 co-ordinate gene expression during neural differentiation. Biochem Soc Trans. 2023.
2022
Liang S, Silva JC, Suska O, Lukoszek R, Almohammed R, Cowling VH. CMTR1 is recruited to transcription start sites and promotes ribosomal protein and histone gene expression in embryonic stem cells. Nucleic Acids Res. 2022;50:2905-2922.
Osborne MJ, Volpon L, Memarpoor-Yazdi M, Pillay S, Thambipillai A, Czarnota S, Culjkovic-Kraljacic B, Trahan C, Oeffinger M, Cowling VH, Borden KLB. Identification and Characterization of the Interaction Between the Methyl-7-Guanosine Cap Maturation Enzyme RNMT and the Cap-Binding Protein eIF4E. J Mol Biol. 2022;434:167451.
2021
Bage MG, Almohammed R, Cowling VH, Pisliakov AV. A novel RNA pol II CTD interaction site on the mRNA capping enzyme is essential for its allosteric activation. Nucleic Acids Res. 2021;49(6):3109-3126.
Basu S, Mak T, Ulferts R, Wu M, Deegan T, Fujisawa R, Tan KW, Lim CT, Basier C, Canal B, Curran JF, Drury LS, McClure AW, Roberts EL, Weissmann F, Zeisner TU, Beale R, Cowling VH, Howell M, Labib K, Diffley JFX. Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp14 RNA cap methyltransferase. Biochem J. 2021;478(13):2481-2497.
Galloway A, Kaskar A, Ditsova D, Atrih A, Yoshikawa H, Gomez-Moreira C, Suska O, Warminski M, Grzela R, Lamond AI, Darzynkiewicz E, Jemielity J, Cowling VH. Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation. Nucleic Acids Res. 2021;49(12):6722-6738.
Pearson L-A, Green CJ, Lin D, Petit A-P, Gray DW, Cowling VH, Fordyce EAF. Development of a High-Throughput Screening Assay to Identify Inhibitors of the SARS-CoV-2 Guanine-N7-Methyltransferase Using RapidFire Mass Spectrometry. SLAS Discovery. 2021;26(6):749-756.
Borden KLB, Culjkovic-Kraljacic B, Cowling VH. To Cap it all Off, Again: Dynamic Capping and Recapping of Coding and Non-coding RNAs to Control Transcript Fate and Biological Activity. Cell Cycle. 2021;20(14):1347-1360.
2020
Culjkovic-Kraljacic B, Skrabanek L, Revuelta MV, Gasiorek J, Cowling VH, Cerchietti L, Borden KLB. The eukaryotic translation initiation factor eIF4E elevates steady-state m7G capping of coding and noncoding transcripts. Proceedings of the National Academy of Sciences. 2020;117(43):26773-26783.
Galloway A, Atrih A, Grzela R, Darzynkiewicz E, Ferguson MAJ, Cowling VH. CAP-MAP: cap analysis protocol with minimal analyte processing, a rapid and sensitive approach to analysing mRNA cap structures. Open Biol. 2020;10(2):190306.
Kasprzyk R, Fido M, Mamot A, Wanat P, Smietanski M, Kopcial M, Cowling VH, Kowalska J, Jemielity J. Direct High-Throughput Screening Assay for mRNA Cap Guanine-N7 Methyltransferase Activity. Chemistry. 2020;26(49):11266-11275.
2019
Bueren-Calabuig JA, M GB, Cowling VH, Pisliakov AV. Mechanism of allosteric activation of human mRNA cap methyltransferase (RNMT) by RAM: insights from accelerated molecular dynamics simulations. Nucleic Acids Res. 2019;47(16):8675-8692.
Dunn S, Lombardi O, Lukoszek R, Cowling VH. Oncogenic PIK3CA mutations increase dependency on the mRNA cap methyltransferase, RNMT, in breast cancer cells. Open Biol. 2019;9(4):190052.
Cowling VH. CAPAM: The mRNA Cap Adenosine N6-Methyltransferase. Trends in Biochemical Sciences. 2019;44:183-185.
Galloway A, Cowling VH. mRNA cap regulation in mammalian cell function and fate. Biochimica et Biophysica Acta (BBA) – Gene Regulatory Mechanisms. 2019;1862:270-279.
2018
Inesta-Vaquera F, Chaugule VK, Galloway A, Chandler L, Rojas-Fernandez A, Weidlich S, Peggie M, Cowling VH. DHX15 regulates CMTR1-dependent gene expression and cell proliferation. Life Sci Alliance. 2018;1(3):e201800092.
Kelner A, Tinti M, Guther MLS, Foth BJ, Chappell L, Berriman M, Cowling VH, Ferguson MAJ. The mRNA cap methyltransferase gene TbCMT1 is not essential in vitro but is a virulence factor in vivo for bloodstream form Trypanosoma brucei. PLoS One. 2018;13(7):e0201263.
Varshney D, Lombardi O, Schweikert G, Dunn S, Suska O, Cowling VH. mRNA Cap Methyltransferase, RNMT-RAM, Promotes RNA Pol II-Dependent Transcription. Cell Rep. 2018;23(5):1530-1542.
Jantsch MF, Quattrone A, O’Connell M, Helm M, Frye M, Macias-Gonzales M, Ohman M, Ameres S, Willems L, Fuks F, Oulas A, Vanacova S, Nielsen H, Bousquet-Antonelli C, Motorin Y, Roignant JY, Balatsos N, Dinnyes A, Baranov P, Kelly V, Lamm A, Rechavi G, Pelizzola M, Liepins J, Holodnuka Kholodnyuk I, Zammit V, Ayers D, Drablos F, Dahl JA, Bujnicki J, Jeronimo C, Almeida R, Neagu M, Costache M, Bankovic J, Banovic B, Kyselovic J, Valor LM, Selbert S, Pir P, Demircan T, Cowling V, Schäfer M, Rossmanith W, Lafontaine D, David A, Carre C, Lyko F, Schaffrath R, Schwartz S, Verdel A, Klungland A, Purta E, Timotijevic G, Cardona F, Davalos A, Ballana E, D OC, Ule J, Fray R. Positioning Europe for the EPITRANSCRIPTOMICS challenge. RNA Biol. 2018;15:829-831.
2017
Dunn S, Lombardi O, Cowling VH. c-Myc co-ordinates mRNA cap methylation and ribosomal RNA production. Biochem J. 2017;474(3):377-384.
Aregger M, Cowling VH. Regulation of mRNA capping in the cell cycle. RNA Biology. 2017;14:11-14.
Inesta-Vaquera F, Cowling VH. Regulation and function of CMTR1-dependent mRNA cap methylation. Wiley Interdiscip Rev RNA. 2017;8:ed2017.
2016
Aregger M, Kaskar A, Varshney D, Fernandez-Sanchez ME, Inesta-Vaquera FA, Weidlich S, Cowling VH. CDK1-Cyclin B1 Activates RNMT, Coordinating mRNA Cap Methylation with G1 Phase Transcription. Mol Cell. 2016;61(5):734-746.
Grasso L, Suska O, Davidson L, Gonatopoulos-Pournatzis T, Williamson R, Wasmus L, Wiedlich S, Peggie M, Stavridis MP, Cowling VH. mRNA Cap Methylation in Pluripotency and Differentiation. Cell Rep. 2016;16(5):1352-1365.
Lombardi O, Varshney D, Phillips NM, Cowling VH. c-Myc deregulation induces mRNA capping enzyme dependency. Oncotarget. 2016;7(50):82273-82288.
Varshney D, Petit AP, Bueren-Calabuig JA, Jansen C, Fletcher DA, Peggie M, Weidlich S, Scullion P, Pisliakov AV, Cowling VH. Molecular basis of RNA guanine-7 methyltransferase (RNMT) activation by RAM. Nucleic Acids Res. 2016;44(21):10423-10436.
Young DF, Andrejeva J, Li X, Inesta-Vaquera F, Dong C, Cowling VH, Goodbourn S, Randall RE. Human IFIT1 Inhibits mRNA Translation of Rubulaviruses but Not Other Members of the Paramyxoviridae Family. J Virol. 2016;90(20):9446-9456.
Research Scientist
Rajaei Almohammed
I am a postdoctoral researcher interested in understanding the RNA cap regulation in neurons. My research involves using lab-grown neurons derived from induced pluripotent stem cells to investigate mRNA localisation and translation. Outside the lab, I enjoy nature walks and scuba diving.
Research Scientist
Veronica DeJesus
I am a postdoctoral researcher looking at the regulation of RNA capping enzymes. My focus is on the cap methyltransferase CMTR1 in embryonic stem cells investigating functional patterns to its interactions with RNA.
Before this role, I completed my PhD in Molecular Virology at The University of Leeds looking at the role of N6-Methyladenosine RNA modification on viral transcript translation and viral replication.
Outside of the lab I enjoy walking my dog in the parks around Glasgow, listening to audiobooks, and tending my shared allotment.
Research Scientist
Dimitrinka Ditsova
I am a postdoctoral researcher who is currently investigating interactions between the transcription factors and RNA, and a dysregulation in T-cell responses in cap methyltransferase deficient cells. I am originally from Bulgaria and moved to Scotland to complete my Bachelor’s in Biochemistry at the University of Dundee. I then decided to stay in Dundee and start my PhD in Professor Vicky Cowling’s lab, initially characterising cap binding proteins in T-cells and then studying the interaction between transcription factors and RNA. During my free time I enjoy reading fantasy books, hiking, cooking and playing video games.
Research Scientist
Alison Galloway
I am an associate scientist researching the regulation of gene expression through RNA processing, stability and translation in immune cells. I’m interested in how the tumour microenvironment affects RNA regulation and how we can enhance tumour immunity by targeting gene expression pathways. I completed my PhD with Martin Turner at the Babraham Institute in Cambridge studying the role of ZFP36 family RNA binding proteins in regulating the cell division cycle in immune cell development. I then joined Vicky Cowling’s laboratory in Dundee as a postdoctoral researcher where I studied the role of RNA cap methyltransferases in inducing gene expression during T cell activation, before moving to the CRUK Scotland Institute to further our studies in the direction of cancer immunity. Outside of the lab I’m a keen kayaker and spend my free time exploring Scotland’s whitewater and coastlines.
Research Scientist
Lydia Hepburn
I am a postdoctoral researcher working on RNMT interactions with proteins and RNA in embryonic stem cells. This has led to having a great interest in RNA secondary structures. I also enjoy gardening, jogging, yoga and attempting to make my own clothes.
Research Scientist
Shang Liang
I am a postdoctoral researcher investigating the roles of RNA cap methyltransferases in glioblastoma. I am interested in the functions of cap methylation in cancer gene expression and the potentials of targeting cap methyltransferases in therapies. Outside the lab, I like going to art galleries and theatres and playing indie puzzle games.
Research Scientist
Jamie Lees*
Information about this team member’s research interests, experience, and background will be added soon. Please check back for updates.
Scientific Officer
Katarzyna Knop
I am a Principal Scientific Officer balancing research leadership with handson science. My current work investigates how CMTR1dependent RNA cap methylation influences Tcell development and function, using mouse genetics and cancer models to uncover new layers of immune regulation.
My scientific path began with a PhD in Molecular Biology at Adam Mickiewicz University in Poznań, where I studied microRNA biogenesis in plants. A Marie SkłodowskaCurie Fellowship then brought me to the University of Dundee to explore RNA 3′end polyadenylation.
In 2021, I pivoted from the RNA tail to the RNA cap, joining Prof. Victoria Cowling’s lab to apply my geneexpression background to mammalian systems.
When I’m not in the lab, you’ll usually find me running, cooking, or discovering new corners of Scotland with my family.
Scientific Officer
Alice Cowley
I am a Senior Scientific Officer investigating the role of mRNA capping enzymes in cancer models. I also explore the functional and phenotypic roles of mutant cap methyltransferase RNMT to further understand its role. Before this role, I completed a Masters in Cancer Research & Precision Oncology at University of Glasgow. Outside of the lab, I enjoy playing football and hillwalking.
Graduate Student
Jacqueline Mills
I am a PhD student working on the regulation of mRNA capping in glioblastoma. My focus is on the cap methyltransferase RNMT, investigating its interaction partners in glioblastoma and how modifying RNMT can alter glioblastoma cellular phenotypes. Before joining the lab, I completed an integrated Master’s degree in Biochemistry at the University of Cambridge. Outside the lab, I enjoy being in nature and reading epic fantasy.
Graduate Student
Thomas Tweedley
I am a PhD student studying RNA capping in T cells. I am trying to better understand how RNA capping enzyme activity and gene specificity are regulated during T cell activation, and how this may affect T cell responses to tumours. Before joining the institute, I completed an integrated Master’s degree specialising in Biochemistry at the University of Cambridge. Outside of the lab, I enjoy running, cycling and hiking.