The RNA 3D Motif Atlas: Computational methods for extraction, organization and evaluation of RNA motifs

Abstract

RNA 3D motifs occupy places in structured RNA molecules that correspond to the hairpin, internal and multi-helix junction “loops” of their secondary structure representations. As many as 40% of the nucleotides of an RNA molecule can belong to these structural elements, which are distinct from the regular double helical regions formed by contiguous AU, GC, and GU Watson-Crick basepairs. With the large number of atomic- or near atomic-resolution 3D structures appearing in a steady stream in the PDB/NDB structure databases, the automated identification, extraction, comparison, clustering and visualization of these structural elements presents an opportunity to enhance RNA science. Three broad applications are: (1) identification of modular, autonomous structural units for RNA nanotechnology, nanobiology and synthetic biology applications; (2) bioinformatic analysis to improve RNA 3D structure prediction from sequence; and (3) creation of searchable databases for exploring the binding specificities, structural flexibility, and dynamics of these RNA elements. In this contribution, we review methods developed for computational extraction of hairpin and internal loop motifs from a non-redundant set of high-quality RNA 3D structures. We provide a statistical summary of the extracted hairpin and internal loop motifs in the most recent version of the RNA 3D Motif Atlas. We also explore the reliability and accuracy of the extraction process by examining its performance in clustering recurrent motifs from homologous ribosomal RNA (rRNA) structures. We conclude with a summary of remaining challenges, especially with regard to extraction of multi-helix junction motifs.

Size-variable zone in V3 region of 16S rRNA

“…These, together with the H3 and H4, form a multihelix conjunction corresponding to the 5 0 domain, also known as the 5-way junction (5 WJ), which is indispensable for 30 S ribosome assembly. 18,20,21 The folded 5 WJ is stabilized, 18 and the assembly of ribosome 30 S is stimulated only after binding the ribosomal protein S4. 22,23 In addition, S4 binding promotes the formation of a crucial pseudoknot structure containing a translation initiation region.…”

Shapeshifting RNAs guide innate immunity

“…Among the nucleic acids, the double-stranded nature of DNA places strong constraints on conformational complexity. In contrast, RNA's ability to form novel base-pairing interactions confers a large degree of structural diversity (2). Such diversity lends itself to the ability to assume multiple metastable structures, i.e.…”

Identification of a GUAAY Pentaloop Sequence Involved in a Novel RNA Loop–Helix Interaction

“…Based on this search, no pentaloop match was identified. However, the RNA 3D Motif Atlas [18, 19] revealed a hexanucleotide loop containing the sequence GUAAU from the eukaryotic thiamine pyrophosphate riboswitch (PDB 3D2V and 2CKY) that docks into a receptor helix in a similar manner as seen in the group IIB1 intron (Figure 2c). In this case, there is no analogous κ-κ′ interaction found near the inserting base stack of the GUAAY sequence, therefore suggesting that this novel loop-receptor combination can exist as an independent functional unit.…”