A comparative analysis of the triloops in all high-resolution RNA structures reveals sequence–structure relationships

Abstract

Despite an increasing number of experimentally determined RNA structures, the gap between the number of structures and that of RNA families is still growing. To overcome this limitation, efficient and reliable RNA modeling methodologies must be developed. In order to reach this goal, here, we show how triloop sequence-structure relationships have been inferred through a systematic analysis of all triloops found in available high-resolution structures. The structural annotation of all triloops allowed us to define discrete states of the triloop's conformational space, and therefore an explicit sequence-to-structure relation. The sequence-structure relationships inferred from this explicit relation are presented in a convenient modeling table that provides a limited set of possible three-dimensional structures given any triloop sequence. The table is indexed by the two nucleotides that form the triloop's flanking base pair, since they are shown to provide the most information about the triloop threedimensional structures. We also report the observations in the X-ray crystallographic structures of important conformational variations, which we believe might be the result of RNA dynamic.

Reverse Watson-Crick purine-purine base pairs — the Sharp-turn motif and other structural consequences in functional RNAs

“…However, an exception is observed in 23S rRNA of H. marismortui and E. coli (context 8 of Table S8), where the uracil of a A:A-U-U quartet co-varies with cytosine. As shown in Figure 7A and B, this quartet mediates a tri-loop tri-loop interaction and therefore, has significant structural roles 69,70 . Interestingly, such substitution of uracil by cytosine involves protonation of either adenine N7 or cytosine N3, which are thermodynamically unfavorable processes under physiological pH (∼7.4) 71 (Table 2).…”

Evidence for Multiple Distinct Interactions between Hepatitis B Virus P Protein and Its Cognate RNA Encapsidation Signal during Initiation of Reverse Transcription

“…However, as in many triloops, the non-planar arrangement of the loop residues, and often also of the closing base-pair, allows for unconventional pairings between all four bases [54]. In addition, numerous different intraloop interactions can occur, as is the case for the HBV ε apical loop ([39] and PDB: 2IXY) and also in numerous triloop sequences found in other RNA 3D structures [55].…”

Improved prediction of RNA tertiary structure with insights into native state dynamics

“…We, therefore, determined the loop propensity for all sequences by generating 20 million random conformations for every possible RNA pyrimidine/purine sequence of length 6 or 7 and stored the fragment sets that were able to meet the planar constraint between the first and last nucleotide in a loop database (Supplemental Table S2). This result may indicate that particular sequences (such as those commonly found in triloops and tetraloops [Gutell et al 2000;Huang et al 2005;Lisi and Major 2007]) have a greater propensity for looping, and this information could be useful for filtering secondary structure predictions. It is also possible that a bias exists in the PDB or fragment library.…”