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 alpha-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.
St-Onge
Karine
K
Institute for Research in Immunology and Cancer, Université de Montréal, PO Box 6128, Downtown station, Montreal, Quebec H3C 3J7, Canada.
Thibault
Philippe
P
Hamel
Sylvie
S
Major
François
F
D001483:Base Sequence; D003196:Computer Graphics; D004722:Endoribonucleases / Q000494:pharmacology; D005656:Fungal Proteins / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012329:RNA, Bacterial / Q000737:chemistry; D012338:RNA, Ribosomal, 23S / Q000737:chemistry* / Q000187:drug effects; D012276:Ricin / Q000494:pharmacology; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA / Q000379:methods*
D005656:Fungal Proteins; D012329:RNA, Bacterial; D012338:RNA, Ribosomal, 23S; C014801:alpha-sarcin; D012276:Ricin; D004722:Endoribonucleases