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RNA structural motifs can be identified using methods that analyze base–base interactions and the conformation of a structure’s backbone; however, these approaches do not necessarily take into consideration the hydrogen bonds that connect the bases or the networks of inter-connected hydrogen-bonded bases that are found in RNA structures. Large clusters of RNA bases that are tightly inter-connected by a network of hydrogen bonds are expected to be stable and relatively rigid substructures. Such base arrangements could therefore be present as structural motifs in RNA structures, especially when there is a requirement for a highly stable support platform or substructure to ensure the correct folding and spatial maintenance of functional sites that partake in catalysis or binding interactions. In order to test this hypothesis, we conducted a search in available RNA crystallographic structures in the Protein Data Bank database using queries that searched for profiles of bases inter-connected by hydrogen bonds. This method of searching does not require to have prior knowledge of the arrangement being searched. Our search results identified two clusters of six bases that are inter-connected by a network of hydrogen bonds. These arrangements of base sextuples have never been previously reported, thus making this the first report that proposes them as novel RNA tertiary motifs.

Identification of Structural Motifs Using Networks of Hydrogen-Bonded Base Interactions in RNA Crystallographic Structures