Development of solid state NMR methodology to study RNA and protein-RNA complexes

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In this research project we plan to develop novel NMR methodology for structural studies of RNA and RNA-protein complexes by means of solid-state NMR (ssNMR). ssNMR leverages the requirements of moderate size and high solubility that limit structural studies by solution-state NMR, or the necessity of high-resolution diffracting crystals for structure determination by X-ray crystallography. ssNMR has been developing fast in the fields of amyloid fibrils, membrane proteins and large protein complexes; however, significantly fewer studies have been performed on RNA or protein-RNA complexes (RNPs), due to the lack of a general approach to study RNA by ssNMR. Taking advantage of recent development of the NMR hardware, different labeling techniques and modern selective magnetization transfer schemes, we will develop a strategy to determine the structure of RNA by ssNMR. These results will pave the way to study large RNAs and RNPs that cannot be studied either by crystallography or solution-state NMR.