Interestingly, in comparison to FOXRRM wild-type, the F126H mutant appears not to cross-link to G2, consistent with the absence of G mononucleotides (brown) or CG dinucleotides (turquoise) in Figure (Table ). Although we do not have supporting data, nor know of any precedence in literature, it is plausible that the histidine has a different cross-linking preferences to tyrosine or phenylalanine and/or that stacking to the guanosine is changed in this particular binding site. Unexpectedly, a H120 crosslink occured with the three FOXRRM mutants, which was hardly observed in the wilde type FOXRRM (Fig. , Fig. ). Analysis of the oligonucleotide cross-links in Figure strongly suggested that the cross-link occurred with U5. In fact, the NMR structure of FOXRRM-FOXRBE shows that U5 adopts a stacking arrangement with H120, and thus might have been expected to cross-link in the wild type FOXRBE-FOXRRM interaction (Fig. ). Taking these findings together, we propose that π-stacking interactions between aromatic amino acids (e.g. phenylalanine, tyrosine or histidine) and guanosines or uridines are an important pre-requisite for their cross-linking to aromatic side chains, and also to the flanking amino acids.