To characterize protein-RNA recognition at the molecular level, structural biology has turned out to be an indispensable approach. Detailed and direct insights into the mechanism of RNA binding and specificity have emerged from protein-RNA structures, especially from the most abundant RNA recognition motif (RRM). Although this protein domain has a very conserved α-β fold, it can recognize a large number of different RNA sequences and shapes and can be involved in a multitude of biological processes. Here, we report on recent single and multiple RRM-RNA structures and point out those features that provide novel insights into the mechanism of RNA recognition by RRMs. We further outline inherent problems to both NMR spectroscopy and X-ray crystallography methods and review recent strategies that emphasize the need to use both methodologies for more rapid and accurate structure determinations.
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