Molecular basis of mRNA localization and translation control

A common mechanism for achieving mRNA localization is the assembly of RNA-protein complexes that are transported by molecular motors along the cytoskeleton to their cellular destination. My project is to investigate how the IMP family of RNA-binding proteins are able to assemble RNA granules and mediate transport. IMP proteins belong to a conserved protein family, which contain multiple RNA-binding domains. Using a variety of biochemical and structural techniques, I determined the molecular basis of RNA recognition for the IMP3 RRM1+RRM2 domain. While this domain has only modest sequence specificity and affinity in RNA binding, these interactions maybe important in the context of the full-length protein. Additionally, I also developed a single-molecule RNA mobility tethering assay to investigate the role of the IMP RRM domains in RNA transport. Interestingly, tethering of the IMP RRM domains to transcripts results in reduced movement of RNA dots in HeLa cells. The motor responsible for this anchoring, however, has not yet been identified.