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Molecules
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Z-DNA and Z-RNA: from Physical Structure to Biological Function
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Z-DNA and Z-RNA: from Physical Structure to Biological Function

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (15 April 2022) | Viewed by 15353

Special Issue Editors

Dr. Alan Herbert

E-Mail Website
Guest Editor
Department of Pharmacology, School of Medicine, University of Auckland, Auckland 6000, New Zealand
Interests: Z-DNA; Z-RNA; ADAR; Zα; flipons; genetics; immunology
Special Issues, Collections and Topics in MDPI journals
Dr. Beat Rolf Vögeli

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Interests: biophysics; nuclear magnetic resonance; protein and nucleic acid structure and dynamics
Special Issues, Collections and Topics in MDPI journals
Dr. Quentin Vicens

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Genetics, and RNA BioScience Initiative, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Interests: biochemistry; cryo-electron microscopy; molecular biology; ribosome; RNA structure and folding; structure prediction; X-ray crystallography
Special Issues, Collections and Topics in MDPI journals
Dr. Maria S. Poptsova

E-Mail Website
Guest Editor
Bioifnformatics Lab, Big Data and Information Retrieval School, Faculty of Computer Science, National Research University Higher School of Economics, Moscow, Russia
Interests: non-B DNA structures; Z-DNA; quadruplexes; triplexes; machine learning; deep learning
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue celebrates a half-century of discoveries related to the left-handed Z conformations of DNA and RNA. The innovations cover many disciplines. Starting with the crystallization of Z-DNA in 1979, biophysical and biochemical studies have yielded many unanticipated and fascinating insights into this class of higher energy nucleic acid conformations.

Recent discoveries of biological functions for left-handed Z-conformations have demonstrated important roles in immunity against infectious agents and cancers. More generally, research on Z conformations underscores the impact of alternative DNA and RNA conformations in both normal cellular function and disease. They further emphasize that regulatory information is encoded by structure in addition to the sequence.

This joint Special Issue between two flagship MDPI journals — Molecules and the International Journal of Molecular Sciences — intends to summarize the status of Z-DNA and Z-RNA research. With this collection, we aim to help build collaborations across the many disciplines that study these conformations and their implications in biology.

We invite authors to help develop a roadmap to guide future discoveries by submitting a review at the leading edge of their respective fields, to either Molecules or IJMS, according to their preference, as well as journal aims and scopes.

We also wish to encourage all to join us for the first virtual ABZ meeting we will be organizing on May 19, 2021 (more on that soon).

Prof. Dr. Alan Herbert
Dr. Beat Rolf Vögeli
Dr. Quentin Vicens
Dr. Maria S. Poptsova
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ADAR
  • auto-immune disease
  • cancer
  • gene regulation
  • Z-DNA
  • Z-RNA
  • Zα
  • ZBP1
  • flipons
  • viral immunity
  • base modification
  • topology
  • DNA repeats

Related Special Issue

Published Papers (4 papers)

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Research

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18 pages, 3344 KiB  
Article
Lone Pair…π Contacts and Structure Signatures of r(UNCG) Tetraloops, Z-Turns, and Z-Steps: A WebFR3D Survey
by Craig L. Zirbel and Pascal Auffinger
Molecules 2022, 27(14), 4365; https://doi.org/10.3390/molecules27144365 - 7 Jul 2022
Cited by 6 | Viewed by 1524
Abstract
Z-DNA and Z-RNA have long appeared as oddities to nucleic acid scientists. However, their Z-step constituents are recurrently observed in all types of nucleic acid systems including ribosomes. Z-steps are NpN steps that are isostructural to Z-DNA CpG steps. Among their structural features, [...] Read more.
Z-DNA and Z-RNA have long appeared as oddities to nucleic acid scientists. However, their Z-step constituents are recurrently observed in all types of nucleic acid systems including ribosomes. Z-steps are NpN steps that are isostructural to Z-DNA CpG steps. Among their structural features, Z-steps are characterized by the presence of a lone pair…π contact that involves the stacking of the ribose O4′ atom of the first nucleotide with the 3′-face of the second nucleotide. Recently, it has been documented that the CpG step of the ubiquitous r(UNCG) tetraloops is a Z-step. Accordingly, such r(UNCG) conformations were called Z-turns. It has also been recognized that an r(GAAA) tetraloop in appropriate conditions can shapeshift to an unusual Z-turn conformation embedding an ApA Z-step. In this report, we explore the multiplicity of RNA motifs based on Z-steps by using the WebFR3D tool to which we added functionalities to be able to retrieve motifs containing lone pair…π contacts. Many examples that underscore the diversity and universality of these motifs are provided as well as tutorial guidance on using WebFR3D. In addition, this study provides an extensive survey of crystallographic, cryo-EM, NMR, and molecular dynamics studies on r(UNCG) tetraloops with a critical view on how to conduct database searches and exploit their results. Full article
(This article belongs to the Special Issue Z-DNA and Z-RNA: from Physical Structure to Biological Function)
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12 pages, 2583 KiB  
Article
Construction of ssDNA-Attached LR-Chimera Involving Z-DNA for ZBP1 Binding Analysis
by Lin Li, Ran An and Xingguo Liang
Molecules 2022, 27(12), 3706; https://doi.org/10.3390/molecules27123706 - 9 Jun 2022
Viewed by 2112
Abstract
The binding of proteins to Z-DNA is hard to analyze, especially for short non-modified DNA, because it is easily transferred to B-DNA. Here, by the hybridization of a larger circular single-stranded DNA (ssDNA) with a smaller one, an LR-chimera (involving a left-handed part [...] Read more.
The binding of proteins to Z-DNA is hard to analyze, especially for short non-modified DNA, because it is easily transferred to B-DNA. Here, by the hybridization of a larger circular single-stranded DNA (ssDNA) with a smaller one, an LR-chimera (involving a left-handed part and a right-handed one) with an ssDNA loop is produced. The circular ssDNAs are prepared by the hybridization of two ssDNA fragments to form two nicks, followed by nick sealing with T4 DNA ligase. No splint (a scaffold DNA for circularizing ssDNA) is required, and no polymeric byproducts are produced. The ssDNA loop on the LR-chimera can be used to attach it with other molecules by hybridization with another ssDNA. The gel shift binding assay with Z-DNA specific binding antibody (Z22) or Z-DNA binding protein 1 (ZBP1) shows that stable Z-DNA can form under physiological ionic conditions even when the extra ssDNA part is present. Concretely, a 5′-terminal biotin-modified DNA oligonucleotide complementary to the ssDNA loop on the LR-chimera is used to attach it on the surface of a biosensor inlaid with streptavidin molecules, and the binding constant of ZBP1 with Z-DNA is analyzed by BLI (bio-layer interferometry). This approach is convenient for quantitatively analyzing the binding dynamics of Z-DNA with other molecules. Full article
(This article belongs to the Special Issue Z-DNA and Z-RNA: from Physical Structure to Biological Function)
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Review

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26 pages, 7706 KiB  
Review
Structure and Formation of Z-DNA and Z-RNA
by Jeffrey B. Krall, Parker J. Nichols, Morkos A. Henen, Quentin Vicens and Beat Vögeli
Molecules 2023, 28(2), 843; https://doi.org/10.3390/molecules28020843 - 14 Jan 2023
Cited by 9 | Viewed by 6998
Abstract
Despite structural differences between the right-handed conformations of A-RNA and B-DNA, both nucleic acids adopt very similar, left-handed Z-conformations. In contrast to their structural similarities and sequence preferences, RNA and DNA exhibit differences in their ability to adopt the Z-conformation regarding their hydration [...] Read more.
Despite structural differences between the right-handed conformations of A-RNA and B-DNA, both nucleic acids adopt very similar, left-handed Z-conformations. In contrast to their structural similarities and sequence preferences, RNA and DNA exhibit differences in their ability to adopt the Z-conformation regarding their hydration shells, the chemical modifications that promote the Z-conformation, and the structure of junctions connecting them to right-handed segments. In this review, we highlight the structural and chemical properties of both Z-DNA and Z-RNA and delve into the potential factors that contribute to both their similarities and differences. While Z-DNA has been extensively studied, there is a gap of knowledge when it comes to Z-RNA. Where such information is lacking, we try and extend the principles of Z-DNA stability and formation to Z-RNA, considering the inherent differences of the nucleic acids. Full article
(This article belongs to the Special Issue Z-DNA and Z-RNA: from Physical Structure to Biological Function)
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16 pages, 3428 KiB  
Review
The Simple Biology of Flipons and Condensates Enhances the Evolution of Complexity
by Alan Herbert
Molecules 2021, 26(16), 4881; https://doi.org/10.3390/molecules26164881 - 12 Aug 2021
Cited by 11 | Viewed by 3359
Abstract
The classical genetic code maps nucleotide triplets to amino acids. The associated sequence composition is complex, representing many elaborations during evolution of form and function. Other genomic elements code for the expression and processing of RNA transcripts. However, over 50% of the human [...] Read more.
The classical genetic code maps nucleotide triplets to amino acids. The associated sequence composition is complex, representing many elaborations during evolution of form and function. Other genomic elements code for the expression and processing of RNA transcripts. However, over 50% of the human genome consists of widely dispersed repetitive sequences. Among these are simple sequence repeats (SSRs), representing a class of flipons, that under physiological conditions, form alternative nucleic acid conformations such as Z-DNA, G4 quartets, I-motifs, and triplexes. Proteins that bind in a structure-specific manner enable the seeding of condensates with the potential to regulate a wide range of biological processes. SSRs also encode the low complexity peptide repeats to patch condensates together, increasing the number of combinations possible. In situations where SSRs are transcribed, SSR-specific, single-stranded binding proteins may further impact condensate formation. Jointly, flipons and patches speed evolution by enhancing the functionality of condensates. Here, the focus is on the selection of SSR flipons and peptide patches that solve for survival under a wide range of environmental contexts, generating complexity with simple parts. Full article
(This article belongs to the Special Issue Z-DNA and Z-RNA: from Physical Structure to Biological Function)
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