Based on the similarity of the cross-linking profiles from U1 and G2 (Fig. ), it seems intuitively likely that guanosines G2 and G6 may follow a similar mechanistic reaction path as U1. Thus, photoexcitation of the stacked guanine-phenyl ring systems produces free radicals at G2 and G6, as well as on the peptide backbone around F126 and F160. Recombination yields direct and indirect cross-links, which in the case of G2 are to the same α-carbon radicals that couple with U1. The nature of the initial exciplex formed from electron-transfer in a stacked guanosine-phenylalanine is unclear, and we were unable to identify a literature precedent for such a mechanism. However, well-cited studies have shown photo-induced electron transfer between π-stacked pyrimidine and purine nucleobases that produce long-lived exciplexes . Electron transfer between an amino acid and a nucleotide might be expected to occur in the direction that yields the lowest-energy exciplex. However, due to the special environment of an RNA-protein binding site (see discussions in refs ), this may not necessarily correlate with the redox potentials of isolated nucleotides or aromatic amino acid side chains. Together, our observations demonstrate the importance of local environment to cross-linking in the RNA-protein binding site, and at least partly explain why cross-links occur only at specific positions in an RNA-RBP motif.