Prof Vicky Cowling, FRSE - Gene Regulation

Introduction

Cowling Vicky 2021

In every human cell, the expression of 25,000 genes is precisely regulated to generate the spectrum of cell types required through development and into the adult. We are interested in the signalling pathways that coordinate and regulate gene expression, and how dysregulation of these pathways is a cause or consequence of disease. Our aim is to understand how gene expression is regulated in health and disease, and to use this knowledge to develop and refine therapeutic approaches.

Our focus is on the RNA cap, a structure found on pre-mRNA and non-coding RNA that protects RNA and recruits factors involved in processing and translation. A series of RNA capping enzymes catalyses cap formation, predominantly as the transcript is being synthesised. We are interested in how these RNA capping enzymes are regulated during development and in the adult, and the impact that this has on gene expression. Currently, we are investigating RNA cap regulation in embryonic stem cell differentiation, during T cell activation and following oncogene dysregulation in cancer models.

Regulation of the RNA cap can have potent effects on cell function and fate decisions via the regulation of specific gene families. We characterise the biochemical configuration of capping enzyme complexes in different cell types or disease states, follow how these configurations change during differentiation and disease, and determine the impact on gene expression and cell function and fate decisions.

Other funding:

Lab Report

pdf Cowling Lab Report (143 KB)

Key Publications

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.

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.

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.

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.

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.