Abstract
RBM10 is a developmental factor whose mis-regulation activates pathways important in tumor progression, such as the Notch pathway. Let-7 is an important tumour suppressor miRNA that downregulates the Myc and Ras genes. It has been recently shown that RBM10 interacts with the pre-Let-7 miRNA, and reduces the cellular concentration of functional Let-7. We will clarify the molecular basis underlying the RBM10-pre-let-7 recognition, and design conservative point mutations that target specifically this interaction. We will then use these mutations in cancer cells to de-convolute the different molecular functions of the protein and understand Let-7-mediated RBM10 regulation in cancer cells.
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