The role of 3' untranslated region variation in the molecular pathogenesis of motor neurone disease

3' untranslated regions (3' UTRs) play critical roles in the control of mRNA translation and stability by presenting sequence motifs and secondary structural elements that mediate interactions between the mRNA and other factors such as proteins or miRNAs. Recent studies have demonstrated that human genetic variations in UTRs and variations in promoter sequences impact upon gene expression to a similar degree. Professors Luscombe and Ule hypothesise that 3' UTR sequence variation disrupts mRNA stability and translation, which can contribute to the pathogenesis of diseases such as cancer or neurodegeneration. They will use genetic and biochemical investigations in differentiated human motor neurones combined with computational modelling to study the impact of alternative 3' UTRs on health and disease.