title: Revisiting GNRA and UNCG folds: U-turns versus Z-turns in RNA hairpin loops.
abstract: When thinking about RNA three-dimensional structures, coming across GNRA and UNCG tetraloops is perceived as a boon since their folds have been extensively described. Nevertheless, analyzing loop conformations within RNA and RNP structures led us to uncover several instances of GNRA and UNCG loops that do not fold as expected. We noticed that when a GNRA does not assume its "natural" fold, it adopts the one we typically associate with a UNCG sequence. The same folding interconversion may occur for loops with UNCG sequences, for instance within tRNA anticodon loops. Hence, we show that some structured tetranucleotide sequences starting with G or U can adopt either of these folds. The underlying structural basis that defines these two fold types is the mutually exclusive stacking of a backbone oxygen on either the first (in GNRA) or the last nucleobase (in UNCG), generating an oxygen-π contact. We thereby propose to refrain from using sequences to distinguish between loop conformations. Instead, we suggest using descriptors such as U-turn (for "GNRA-type" folds) and a newly described Z-turn (for "UNCG-type" folds). Because tetraloops adopt for the largest part only two (inter)convertible turns, we are better able to interpret from a structural perspective loop interchangeability occurring in ribosomes and viral RNA. In this respect, we propose a general view on the inclination for a given sequence to adopt (or not) a specific fold. We also suggest how long-noncoding RNAs may adopt discrete but transient structures, which are therefore hard to predict.
authors.affiliation: Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, F-67000 Strasbourg, France.
authors.forename: Luigi
authors.identifier: 0000-0002-9780-9134
authors.initials: L
authors.lastname: D'Ascenzo
authors.affiliation: Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, F-67000 Strasbourg, France.|Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Poland.
authors.forename: Filip
authors.identifier: 0000-0002-2563-7169
authors.initials: F
authors.lastname: Leonarski
authors.affiliation: Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, F-67000 Strasbourg, France.
authors.forename: Quentin
authors.identifier: 0000-0003-3751-530X
authors.initials: Q
authors.lastname: Vicens
authors.affiliation: Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, F-67000 Strasbourg, France.
authors.forename: Pascal
authors.identifier: 0000-0002-3816-2721
authors.initials: P
authors.lastname: Auffinger
mesh_terms: D055029:Inverted Repeat Sequences; D008958:Models, Molecular; D059372:Nucleotide Motifs; D059370:RNA Folding; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D012367:RNA, Viral
keywords: RNA folding; RNA motif; structure prediction; tRNA anticodon; tetraloop