Modeling RNA tertiary structure motifs by graph-grammars

A new approach, graph-grammars, to encode RNA tertiary structure patterns is introduced and exemplified with the classical sarcin–ricin motif. The sarcin–ricin motif is found in the stem of the crucial ribosomal loop E (also referred to as the sarcin–ricin loop), which is sensitive to the α-sarcin and ricin toxins. Here, we generate a graph-grammar for the sarcin-ricin motif and apply it to derive putative sequences that would fold in this motif. The biological relevance of the derived sequences is confirmed by a comparison with those found in known sarcin–ricin sites in an alignment of over 800 bacterial 23S ribosomal RNAs. The comparison raised alternative alignments in few sarcin–ricin sites, which were assessed using tertiary structure predictions and 3D modeling. The sarcin–ricin motif graph-grammar was built with indivisible nucleotide interaction cycles that were recently observed in structured RNAs. A comparison of the sequences and 3D structures of each cycle that constitute the sarcin–ricin motif gave us additional insights about RNA sequence–structure relationships. In particular, this analysis revealed the sequence space of an RNA motif depends on a structural context that goes beyond the single base pairing and base-stacking interactions.