Science

RNA and RNA epigenetics
RNA (ribonucleic acid) is the only direct product of the human genome and as mRNA acts as the template for the synthesis of all proteins, the molecular machines of the cell. RNA is also known to be a key player in cellular decision-making, particularly in the form of non-coding RNA (ncRNA) such as microRNA, piRNA and long non-coding RNA. Almost all of this RNA is chemically modified: over 100 different chemical modifications have been identified to date, catalysed by several large families of RNA-modifying enzymes. The discovery of reversible chemical modifications of RNA and their role in changing RNA activity and regulating key processes within the cell gave rise to the concept of RNA epigenetics. There is a growing understanding of the importance of RNA modifications in the development of cancer and other diseases, providing a wealth of novel therapeutic targets for drug discovery.

STORM target discovery platform and pipeline
At the core of our R&D strategy is a close relationship with our scientific founders at the University of Cambridge. We work hand in hand with their research groups using cutting-edge techniques such as chemical biology, RNA-Seq and RNA mass spectrometry to elucidate the functional role of diverse RNA modifications and identify their protein writers, readers and erasers. We use the latest insights and emerging data from our collaboration to build a unique target discovery platform for the identification of new drug targets. Drawing on our emerging platform, we have established a pipeline of drug discovery programmes to develop novel, first-in-class drugs for the treatment of specific cancers with high unmet medical need.

STORM target discovery platform and pipeline

Learn more about STORM’s scientific founders

Selected publications

An epigenetics gold rush: new controls for gene expression

Willyard C
Nature. 2017 Feb 23;542:406–408

The RNA code comes into focus

Chi KR
Nature. 2017 Feb 23;542:503–506

Transgenerational inheritance: Models and mechanisms of non-DNA sequence-based inheritance

Miska EA, Ferguson-Smith AC
Science. 2016 Oct 7;354(6308):59–63

Formation and abundance of 5-hydroxymethylcytosine in RNA

Huber SM, van Delft P, Mendil L, Bachman M, Smollett K, Werner F, Miska EA, Balasubramanian S
Chembiochem. 2015 Mar 23;16(5):752–5

The breast cancer oncogene EMSY represses transcription of antimetastatic microRNA miR-31

Viré E, Curtis C, Davalos V, Git A, Robson S, Villanueva A, Vidal A, Barbieri I, Aparicio S, Esteller M, Caldas C, Kouzarides T
Mol Cell. 2014 Mar 6;53(5):806–18

2'-O-Methyl-5-hydroxymethylcytidine: A Second Oxidative Derivative of 5-Methylcytidine in RNA

Huber SM, van Delft P, Tanpure A, Miska EA, Balasubramanian S
J Am Chem Soc. 2017 Jan 25

miR-182 Regulates Slit2-Mediated Axon Guidance by Modulating the Local Translation of a Specific mRNA

Bellon A, Iyer A, Bridi S, Lee FC, Ovando-Vázquez C, Corradi E, Longhi S, Roccuzzo M, Strohbuecker S, Naik S, Sarkies P, Miska E, Abreu-Goodger C, Holt CE, Baudet ML
Cell Rep. 2017 Jan 31;18(5):1171–1186

BET inhibitor resistance emerges from leukaemia stem cells

Fong CY, Gilan O, Lam EY, Rubin AF, Ftouni S, Tyler D, Stanley K, Sinha D, Yeh P, Morison J, Giotopoulos G, Lugo D, Jeffrey P, Lee SC, Carpenter C, Gregory R, Ramsay RG, Lane SW, Abdel-Wahab O, Kouzarides T, Johnstone RW, Dawson SJ, Huntly BJ, Prinjha RK, Papenfuss AT, Dawson MA
Nature. 2015 Sep 24;525(7570):538–42

Histone core modifications regulating nucleosome structure and dynamics

Tessarz P, Kouzarides T
Nat Rev Mol Cell Biol. 2014 Nov;15(11):703–8