Molecular basis of RNA regulation networks
We investigate the regulation of mRNA transport and local translation in neuronal development and function. Establishing and maintaining the complex network of connections required for neuronal communication requires the regulated transport of hundreds to thousands of mRNAs to specific locations in the cell and their in situ translation. RNA-binding proteins mediate the interaction of the mRNAs with the machines of cellular transport, as well as the regulation of the mRNAs' translation control. Our research strategy is guided by the central role played by the RNA-binding proteins. We ask how these proteins select their mRNA targets in the cell and interface with the motors on the microtubules network. We also ask how these interactions and the mRNAs' translation are regulated by signalling. We use a combination of newly designed and established structural and biophysical methods to look at the large and flexible protein-RNA complexes, including novel NMR methods based on cross-saturation, CSP and PRE. We combine the output of these molecular investigations with transcriptome-wide data on the interactions to build mechanistic models to describe the function of the proteins. We apply the same approach to investigate a second, related, area of research, the selective regulation of miRNA biogenesis and transport.
