RNA structural motifs that entail hydrogen bonds involving sugar–phosphate backbone atoms of RNA

Abstract

The growing number of high-resolution crystal structures of large RNA molecules provides much information for understanding the principles of structural organization of these complex molecules. Several in-depth analyses of nucleobase-centered RNA structural motifs and backbone conformations have been published based on this information, including a systematic classification of base pairs by Leontis and Westhof. However, hydrogen bonds involving sugar–phosphate backbone atoms of RNA have not been analyzed systematically until recently, although such hydrogen bonds appear to be common both in local and tertiary interactions. Here we review some backbone structural motifs discussed in the literature and analyze a set of eight high-resolution multi-domain RNA structures. The analyzed RNAs are highly structured: among 5372 nucleotides in this set, 89% are involved in at least one “long-range” RNA–RNA hydrogen bond, i.e., hydrogen bonds between atoms in the same residue or sequential residues are ignored. These long-range hydrogen bonds frequently use backbone atoms as hydrogen bond acceptors, i.e., OP1, OP2, O2′, O3′, O4′, or O5′, or as a donor (2′OH). A surprisingly large number of such hydrogen bonds are found, considering that neither single-stranded nor double-stranded regions will contain such hydrogen bonds unless additional interactions with other residues exist. Among 8327 long-range hydrogen bonds found in this set of structures, 2811, or about one-third, are hydrogen bonds entailing RNA backbone atoms; they involve 39% of all nucleotides in the structures. The majority of them (2111) are hydrogen bonds entailing ribose hydroxyl groups, which can be used either as a donor or an acceptor; they constitute 25% of all hydrogen bonds and involve 31% of all nucleotides. The phosphate oxygens OP1 or OP2 are used as hydrogen bond acceptors in 12% of all nucleotides, and the ribose ring oxygen O4′ and phosphodiester oxygens O3′ and O5′ are used in 4%, 4%, and 1% of all nucleotides, respectively. Distributions of geometric parameters and some examples of such hydrogen bonds are presented in this report. A novel motif involving backbone hydrogen bonds, the ribose–phosphate zipper, is also identified.