Project at a glance

The impact of 5’UTR mRNA heterogeneity on the mammalian proteome

Our lab is interested in understanding how 5’UTR heterogeneity impacts on the translational readout and how perturbations in its regulation, either at the level of promoter usage and/or alternative splicing, can disrupt normal cellular function.

Initially we focused on two model systems, namely, the tumour suppressor gene MDM2 in which heterogeneity arises due to the use of alternative promoters, and the transcription factor ELK1 in which it arises as a result of alternative splicing. However, recently we have begun genome wide RNAseq analysis of total and polysomal mRNA populations in human tumours (employing both polysomal and ribosomal profiling) with the aim of dissecting the impact of changes in the 5’UTR variant profile on the tumoural phenotype.