Effects of Noncanonical Base Pairing on RNA Folding: Structural Context and Spatial Arrangements of G·A Pairs

Noncanonical
base pairs play important roles in assembling the
three-dimensional structures critical to the diverse functions of
RNA. These associations contribute to the looped segments that intersperse
the canonical double-helical elements within folded, globular RNA
molecules. They stitch together various structural elements, serve
as recognition elements for other molecules, and act as sites of intrinsic
stiffness or deformability. This work takes advantage of new software
(DSSR) designed to streamline the analysis and annotation of RNA three-dimensional
structures. The multiscale structural information gathered for individual
molecules, combined with the growing number of unique, well-resolved
RNA structures, makes it possible to examine the collective features
deeply and to uncover previously unrecognized patterns of chain organization.
Here we focus on a subset of noncanonical base pairs involving guanine
and adenine and the links between their modes of association, secondary
structural context, and contributions to tertiary folding. The rigorous
descriptions of base-pair geometry that we employ facilitate characterization
of recurrent geometric motifs and the structural settings in which
these arrangements occur. Moreover, the numerical parameters hint
at the natural motions of the interacting bases and the pathways likely
to connect different spatial forms. We draw attention to higher-order
multiplexes involving two or more G·A pairs and the roles these
associations appear to play in bridging different secondary structural
units. The collective data reveal pairing propensities in base organization,
secondary structural context, and deformability and serve as a starting
point for further multiscale investigations and/or simulations of
RNA folding.