Prof Vicky Cowling

Gene Regulation

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.

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Biography

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Recent Publications

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Biography

Education and qualifications

2002: PhD, Cancer Research UK London Research Institute/UCL – Caspase activation during programmed cell death
1997: BA Natural Sciences, Cambridge University

Appointments

2025–present: Deputy Director, CRUK Scotland Institute, Glasgow, UK
2022–present: Senior Group Leader, CRUK Scotland Institute, Glasgow, UK and Chair of Biology (Full Professor), University of Glasgow, UK
2017–2022: Deputy Head of Centre for Gene Regulation and Expression, University of Dundee, UK
2016: Chair of Biology (Full Professor), University of Dundee, UK
2007–2022: Group Leader, School of Life Sciences, University of Dundee, UK – Regulation of RNA cap in health and disease
2003–2007: Postdoctoral research at Princeton University and Darmouth College, USA – Myc oncogenes: mechanisms and function in breast cancers

Awards and fellowships

Wellcome Trust Investigator Award, 2020
Fellow of the Royal Society of Edinburgh, 2019
Wolfson Royal Society Research Merit Award, 2018
European Research Council (ERC) Consolidator Award, 2017
Fellow of the Royal Society of Biology (UK), 2016
British Society of Cell Biology Women in Cell Biology Award, 2015
European Molecular Biology Organisation (EMBO) Young Investigator, 2014
Medical Research Council UK (MRC) Senior Fellowship, 2013
Lister Institute Prize Fellowship, 2011
Medical Research Council UK (MRC) Career Development Award, 2007

Current committee membership

British Society of Cell Biology Committee
Wellcome Trust Expert Review Group
Volkswagen Foundation Momentum Panel
Royal Society of Edinburgh Fellow Selection Panel

Funding

Wellcome Trust

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.