Professor IC Eperon

I studied Biochemistry at the University of Bristol from 1974 to 1977 and then worked for my PhD with Dr Fred Sanger at the MRC Laboratory of Molecular Biology Cambridge. This was followed by a year of post-doctoral work in the same laboratory. Following this I went to Yale for 2 years (1982-3) on an SERC-NATO fellowship to work with Prof. Joan Steitz on RNA splicing. I began at Leicester as a lecturer in 1984 and was appointed as a Reader and then Professor of Biochemistry.

Almost all mammalian genes produce multiple isoforms of mRNA and protein by alternative splicing. We are interested in the molecular mechanisms by which sites are selected. There are lots of candidate sites in the pre-mRNA. Some are used constitutively, some in specific circumstances, some only if the normal site is mutated, and others never. How is the RECOGNITION by specific factors turned into SELECTION of a site? This process involves many RNA-binding proteins that appear to compete or collaborate in binding, with low and often overlapping specificities. To understand recognition and selection, we need to understand what the pre-mRNA looks like: which proteins are bound, where, and in what numbers, and what effects they have on the behaviour of the RNA.

We have adopted a multi-disciplinary approach to this very challenging question, based on a combination of single molecule total internal reflection fluorescence microscopy with novel chemical biology tools. This is facilitated by a BBSRC sLoLa award that supports a consortium including colleagues in Leicester, Glasgow and Strathclyde with expertise in optics, structural biology, bio-organic chemistry and nano-engineering..

(0) Eperon, I.C., Anderson, S. and Nierlich, D.P. (1980). Distinctive sequence of human mitochondrial ribosomal RNA genes. Nature 286, 460-467.

Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J., Staden, R., and Young, I. G.(1981). The sequence and organisation of the human mitochondrial genome. Nature 290, 457-467. 

Eperon, L.P., Estibeiro, J.P. and Eperon, I.C. (1986). The role of nucleotide sequences in splice site selection in eukaryotic pre-messenger RNA. Nature 324, 280-282.

Eperon, L.P., Graham, I.R., Griffiths, A.D. and Eperon, I.C. (1988). The effects of RNA secondary structure on alternative splicing of pre-mRNA: is folding limited to a region behind the transcribing RNA polymerase? Cell 54, 393-401.

Eperon, I.C., Ireland, D.C., Smith, R.A., Mayeda, A., and Krainer, A.R. (1993). Pathways for selection of 5' splice sites by U1 snRNPs and SF2/ASF. EMBO J. 12, 3607-3617.

Venables, J.P., Elliott, D.J., Makarova, O.V., Makarov, E.M., Cooke, H.J,.& Eperon, I.C. (2000). RBMY, a probable human spermatogenesis factor, and other hnRNP G proteins interact with Tra2b and affect splicing. Hum. Mol. Gen. 9, 685-694.

Eperon, I.C., Makarova, O., Mayeda, A., Munroe, S.H., Cáceres, J., Hayward, D.G., & Krainer, A.R. (2000) Selection of alternative 5' splice sites: the role of U1 snRNP and models for the antagonistic affects of SF2/ASF and hnRNP A1. Mol. Cell. Biol. 20, 8303-8318.

Skordis, L.A., Dunckley, M.G., Yue, B.-G., Eperon, I.C., and Muntoni, F. (2003). Bifunctional antisense oligonucleotides provide a trans-acting splicing enhancer that stimulates SMN2 gene expression in patient fibroblasts. Proc. Natl Acad. Sci. USA 100, 4114-4119. 

Cherny, D., Gooding, C., Eperon, G.E., Coelho, M.B., Bagshaw, C.R., Smith, C.W.J., & Eperon, I.C. (2010). Stoichiometry of a regulatory splicing complex revealed by single molecule analyses. EMBO J. 29, 2161-2172.

Weldon, C., Behm-Ansmant, I., Hurley, L.H., Burley, G.A., Branlant, C., Eperon, I.C., and Dominguez, C. (2017). Identification of G-quadruplexes in functional RNAs using 7-deaza-guanine. Nature Chemical Biology 13, 18-20.

Jobbins, A.M., Reichenbach, L.F., Lucas, C.M., Hudson, A.J., Burley, G.A., & Eperon, I.C. (2018). The mechanisms of a mammalian splicing enhancer. Nucleic Acids Research 46, 2145-2158. 

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Mechanisms of splice site selection/ single molecule microscopy/applications of chemical biology

BS3010: Gene expression: molecular basis and medical relevance
BS2091: From genes to proteins

RNA splicing