Journal Article

‘Z-DNA like’ fragments in RNA: a recurring structural motif with implications for folding, RNA/protein recognition and immune response

Luigi D'Ascenzo, Filip Leonarski, Quentin Vicens and Pascal Auffinger

in Nucleic Acids Research

Volume 44, issue 12, pages 5944-5956
Published in print July 2016 | ISSN: 0305-1048
Published online May 2016 | e-ISSN: 1362-4962 | DOI: https://dx.doi.org/10.1093/nar/gkw388

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Since the work of Alexander Rich, who solved the first Z-DNA crystal structure, we have known that d(CpG) steps can adopt a particular structure that leads to forming left-handed helices. However, it is still largely unrecognized that other sequences can adopt ‘left-handed’ conformations in DNA and RNA, in double as well as single stranded contexts. These ‘Z-like’ steps involve the coexistence of several rare structural features: a C2’-endo puckering, a syn nucleotide and a lone pair–π stacking between a ribose O4’ atom and a nucleobase. This particular arrangement induces a conformational stress in the RNA backbone, which limits the occurrence of Z-like steps to ≈0.1% of all dinucleotide steps in the PDB. Here, we report over 600 instances of Z-like steps, which are located within r(UNCG) tetraloops but also in small and large RNAs including riboswitches, ribozymes and ribosomes. Given their complexity, Z-like steps are probably associated with slow folding kinetics and once formed could lock a fold through the formation of unique long-range contacts. Proteins involved in immunologic response also specifically recognize/induce these peculiar folds. Thus, characterizing the conformational features of these motifs could be a key to understanding the immune response at a structural level.

Journal Article.  8065 words.  Illustrated.

Subjects: Chemistry ; Biochemistry ; Bioinformatics and Computational Biology ; Genetics and Genomics ; Molecular and Cell Biology