Multiple non-canonical base-stacking interactions as one of the major determinants of RNA tertiary structure organization

Abstract

Interplane (stacking) interactions of heterocyclic bases of nucleotide residues (n.t.) of RNA are one of the most important factors in the organization of its secondary and tertiary structure. Most of these (canonical) interactions are carried out between neighbors in the polynucleotide chains of RNA. However, with the accumulation of data on the atomic tertiary structures of a wide variety of RNAs and their complexes with proteins, it became clear that RNA nucleotide residues that are not neighbors in their polynucleotide chains and are sometimes separated in the RNA primary structure by tens or hundreds of n.t. can interact with the help of base stacking (non-canonical). This paper presents an exhaustive database of such elements and their environment in the macromolecules of natural and synthetic RNAs. They were called nonadjacent base-stacking elements (NA-BSE). The analysis of these data showed that the NA-BSE forming nucleotides, on average, account for about a quarter of all nucleotides of a particular RNA, therefore, they should be considered as real motifs in their tertiary structure. The classification of NA-BSE by types of localization in RNA macromolecules is carried out. It is shown that the structure-forming role of NA-BSE consists in the compact folding of single-stranded RNA loops, in the transformation of double-stranded bulges into imperfect helices, as well as in the binding of RNA regions removed in their primary and secondary structure.