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

Abstract

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.

Annotation of the local context of RNA secondary structure improves the classification and prediction of A-minors

“…In Nissen et al (2001) , authors describe a motif called A-patch that is formed by a stack of adenines involved in A-minors. In Hamdani and Firdaus-Raih (2019) , such A-patches of two stacked adenines and two consecutive base pairs have been introduced as sextuples, a novel RNA tertiary motif composed of six bases interconnected with hydrogen bonds. Usually, “A-minor interaction” or just “A-minor” are used to refer to an individual nucleotide triple (one adenine and one base pair), and the term “A-minor motif” is used to describe a cluster of two and more A-minor interactions ( Hendrix et al 2005 ).…”

Graph Theoretical Methods and Workflows for Searching and Annotation of RNA Tertiary Base Motifs and Substructures

“…In cases where such arrangements have not been reported, the discovery of a novel base arrangement motif will have been achieved. This particular approach utilizes the COGNAC computer program [26,49].…”

Special Issue Editorial: Chemical Bonding in Crystals and Their Properties

“…Unlike the other papers in this Issue, reference [6] focuses on intermolecular interactions and supramolecular associates found in crystals of RNA. An analysis of H-bond connected sextuples of RNA bases collected in the Protein Data Bank and relative occurrences of the sextuples allowed the authors of [6] to classify some of them as a novel RNA tertiary motif.…”