RNA approaches the B‐form in stacked single strand dinucleotide contexts

Abstract

Duplex RNA adopts an A-form structure, while duplex DNA interconverts between the A- and B-forms depending on the environment. The C2'-endo sugar pucker seen in B-form DNA can occur infrequently in ribose sugars as well, but RNA is not understood to assume B-form conformations. Through analysis of over 45,000 stacked single strand dinucleotide (SSD) crystal structure conformations, this study demonstrates that RNA is capable of adopting a wide conformational range between the canonical A- and B-forms at the localized SSD level, including many B-form-like conformations. It does so through C2'-endo ribose conformations in one or both nucleotides, and B-form-like neighboring base stacking patterns. As chemical reactions on nucleic acids involve localized changes in chemical bonds, the understanding of how enzymes distinguish between DNA and RNA nucleotides is altered by the energetic accessibility of these rare B-form-like RNA SSD conformations. The existence of these conformations also has direct implications in parametrization of molecular mechanics energy functions used extensively to model nucleic acid behavior., 2016. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 65-82, 2016.

The extent of B-form structure in a 6S RNA variant that mimics DNA to bind to the Escherichia coli RNA Polymerase

“…If all SSDs are simply separated into ones relatively closer to the A-form or the B-form, then a majority of the SSDs are clustered near the canonical A-form, but some SSDs clearly cross over to the B-form, mostly in conformational regions further away from the canonical B-form. This behavior was also observed in our larger crystallographic survey, 3 such that crossing over to the B-form region seems to be easier for RNA if it moves away from both canonical forms, and the region very close to the canonical B-form structure does not seem to be accessible.…”

“…3 This 6S RNA* structure therefore suggests that RNA 3 . CC-BY-NC-ND 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

“…3 This analysis does not require duplex structures, and can assess relative proximity to A-and B-form structures at a local or global level. We showed that RNA SSDs approach a B-form structure in many instances, 3 and this local B-form structure seems to be achieved through both C2 -endo sugar conformations or base stacking patterns that resemble B-form DNA stacking.…”

“…3 This analysis does not require duplex structures, and can assess relative proximity to A-and B-form structures at a local or global level. We showed that RNA SSDs approach a B-form structure in many instances, 3 and this local B-form structure seems to be achieved through both C2 -endo sugar conformations or base stacking patterns that resemble B-form DNA stacking. 4 Interestingly, the base RMSD values show a greater propensity for B-form structures than the sugar-phosphate backbone at the SSD level, which suggests an under-representation of B-form-like sugar-phosphate conformations for RNA in the PDB models.…”

Geometric Patterns for Neighboring Bases Near the Stacked State in Nucleic Acid Strands

“…This is illustrated by our recent discovery of previously unreported B-form conformations in RNA singlestrand dinucleotide (SSD) contexts, which are geometrically separable from the A-form population in individual RNA SSD dinucleotide sequences. 34 The precise pattern of SSD stacking can have functional consequences; for example, it influences the effect of radiation on nucleic acid bases. 35,36 DNA helices containing a covalent linkage between neighboring thymines in an SSD (thymine dimers) show large deviations from canonical helical geometries.…”