RNA splicing

RNA splicing is a major contributor to protein diversity and genetic regulation operating in eukaryotic cells. Splicing is poorly understood at the mechanistic level, which limits our capacity to fully understand how genetic diversity is regulated.

Furthermore, many splicing events result in isoforms that produce proteins of altered or even antagonistic function. Exogenous manipulation of splicing could therefore provide new opportunities for therapeutic development.
On-going efforts in the group focus the development of chemical biological methods to:
  • Understand the molecular mechanisms of splice site selection.
  • Identify small molecules and oligonucleotides that manipulate splicing.
  • Probe how splicing proteins regulate splicing.
Relevant Publications Collaboration
Smith, L.D., Dickinson, R.L, Lucas,C.M., Cousins, A., Malygin, A.A., Weldon, C., Perrett, A.J., Bottrill, A.R., Searle, M.S., Burley, G.A.*, Eperon, I.C.* "A targeted oligonucleotide enhancer of SMN2 exon 7 splicing forms competing quadruplex and protein complexes in functional conditions" Cell Reports, 2014, 9, 193-205. [link]

Perrett, A.J.; Dickinson, R.L.; Krpetic, Z., Brust, M.; Lewis, H.; Eperon, I.C.; Burley, G.A. "Conjugation of PEG and gold nanoparticles to increase the accessibility and valency of tethered RNA splicing enhancers" Chemical Science, 2013, 4, 257-265. [link]

Lewis, H.; Perrett, A.J.; Burley, G.A.; Eperon, I.C. "An RNA splicing enhancer that does not act by looping" Angewandte Chemie International Edition, 2012, 39, 9800-9803. [link]

Prof. Ian C. Eperon
Dr. Cyril Dominguez
further reading
General overview of RNA splicing
General overview of RNA splicing (2)