title: 'Z-DNA like' fragments in RNA: a recurring structural motif with implications for folding, RNA/protein recognition and immune response.
abstract: 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.
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg 67084, France.
authors.forename: Luigi
authors.initials: L
authors.lastname: D'Ascenzo
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg 67084, France Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
authors.forename: Filip
authors.initials: F
authors.lastname: Leonarski
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg 67084, France q.vicens@ibmc-cnrs.unistra.fr.
authors.forename: Quentin
authors.identifier: 0000-0003-3751-530X
authors.initials: Q
authors.lastname: Vicens
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg 67084, France p.auffinger@ibmc-cnrs.unistra.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Auffinger
mesh_terms: D020029:Base Pairing; D043542:DNA, Z-Form / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007700:Kinetics; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D059370:RNA Folding; D016337:RNA, Catalytic / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D012270:Ribosomes / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D058928:Riboswitch / Q000235:genetics* / Q000276:immunology; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D043542:DNA, Z-Form; D016337:RNA, Catalytic; D058928:Riboswitch; D012313:RNA