RNA backbone is rotameric

Abstract

Despite the importance of local structural detail to a mechanistic understanding of RNA catalysis and binding functions, RNA backbone conformation has been quite recalcitrant to analysis. There are too many variable torsion angles per residue, and their raw empirical distributions are poorly clustered. This study applies quality-filtering techniques (using resolution, crystallographic B factor, and all-atom steric clashes) to the backbone torsion angle distributions from an 8,636-residue RNA database. With noise levels greatly reduced, clear signal appears for the underlying angle preferences. Half-residue torsion angle distributions for ␣-␤-␥ and for ␦--are plotted and contoured in 3D; each shows about a dozen distinct peaks, which can then be combined in pairs to define complete RNA backbone conformers. Traditional nucleic acid residues are defined from phosphate to phosphate, but here we use a base-to-base (or sugar-to-sugar) division into ''suites'' to parse the RNA backbone repeats, both because most backbone steric clashes are within suites and because the relationship of successive bases is both reliably determined and conformationally important. A suite conformer has seven variables, with sugar pucker specified at both ends. Potential suite conformers were omitted if not represented by at least a small cluster of convincing data points after application of quality filters. The final result is a small library of 42 RNA backbone conformers, which should provide valid conformations for nearly all RNA backbone encountered in experimental structures.RNA structure ͉ RNA conformation ͉ backbone conformers ͉ quality filtering ͉ all-atom contacts R NA has long been known to play a central role in the storage, and especially in the communication, of biological information and to be well-suited for specific and regulated molecularbinding interactions. More recently, it has also been shown to perform enzymatic catalysis (1, 2) and is therefore quite likely to have been critical in the first development of living systems (3). The size, complexity, and specific detail of RNA 3D structure are essential to its various functions, and in that respect RNA is more like protein than like DNA. The determination, analysis, and modification of RNA structure have become an important aspect of biology, with major contributions from NMR (4), electron microscopy (5), and crystallography (6). Progress accelerated recently with the tour-de-force x-ray structures of the ribosomal 50S and 30S (7-9) subunits, which expanded the database of known RNA structures enough to make statistical analysis feasible.Despite all the new information, determining and analyzing RNA structure are both still very difficult tasks. Large RNA structures can typically be determined only to resolutions of Ϸ2.5 Å or lower, where the phosphates and base planes can be located quite reliably, but the sugars and especially the rest of the backbone are not seen well at all. As shown in Fig. 1, there are six rotatable torsion angles per residue along the RNA backbon...

RNA backbone: Consensus all-angle conformers and modular string nomenclature (an RNA Ontology Consortium contribution)

“…A representative example is listed for each conformer, chosen by stringent combined criteria described in the Materials and Methods section. Columns 6-8 give the equivalent cluster identifiers from the Fourier-averaging update of Schneider et al (2004), the all-angle suite name from Murray et al (2003), and the binned-angle names from the suite-based reworking of Hershkovitz et al (2003); see the ''Updates and reanalyses of empirical clustering'' section in the Materials and Methods for details. The 7D dihedral-angle mean values for each cluster are given in degrees, with standard deviations in parentheses.…”

“…Examples are numbered according to the central P of the suite (=second base). ''Dinuc'' is the updated equivalents to Schneider et al (2004); ''Suite'' is taken from Murray et al (2003); ''Bin'' is the suite-binned equivalent to Hershkovitz et al (2003) (see text).…”

“…to pseudo-objects with locations and orientations. Murray et al (2003) proposed the sugar-to-sugar ''suite'' unit (see Fig. 1), which relates successive bases and within which fitting errors are more easily diagnosed; they developed a large RNA database filtered at the suite level by resolution, crystallographic Bfactor, and all-atom steric clashes, then studied the multidimensional dihedral-angle distribution and defined 42 backbone suite rotamers.…”

RNA structural motifs: building blocks of a modular biomolecule

“…A web server providing a sophisticated annotation of secondary structures and some tertiary interactions has been presented by Major and co-workers (Gendron et al 2001). Conformational analysis of the RNA backbone using reduced representations has also been used to characterize known motifs (Duarte & Pyle, 1998 ;Duarte et al 2003 ;Hershkovitz et al 2003 ;Murray et al 2003) and even identify new motifs (Wadley & Pyle, 2004). Cluster analysis of root-mean-square deviations between pairs of RNA fragments has been used as the basis for cluster analysis of RNA loop structures to group tetraloops into various families (Huang et al 2005).…”

FR3D: finding local and composite recurrent structural motifs in RNA 3D structures

“…Several different representations of RNA backbone conformations have been introduced to search for, analyze, and classify recurrent RNA 3D conformations [9,10,18,37,38,41,43]. In general, backbone search methods are relatively fast and can be automated to find new recurrent motifs [43].…”