The hnRNP K-homology (KH) domain is a single stranded nucleic acid binding domain that mediates RNA target recognition by a large group of gene regulators. The structure of the KH fold is well characterised and some initial rules for KH-RNA recognition have been drafted. However, recent findings have shown that these rules need to be revisited and have now provided a better understanding of how the domain can recognise a sequence landscape larger than previously thought as well as revealing the diversity of structural expansions to the KH domain. Finally, novel structural and functional data show how multiple KH domains act in a combinatorial fashion to both allow recognition of longer RNA motifs and remodelling of the RNA structure. These advances set the scene for a detailed molecular understanding of KH selection of the cellular targets.
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