Special Issue: A, B and Z: The Structure, Function and Genetics of Z-DNA and Z-RNA.

Alan Herbert,Karen M Vasquez,Maria Poptsova,Sergey Karapetyan,Beat Vögeli,Quentin Vicens

doi:10.3390/ijms22147686

Abstract

It is now difficult to believe that a biological function for the left-handed Z-DNA and Z-RNA conformations was once controversial. The papers in this Special Issue, “Z-DNA and Z-RNA: from Physical Structure to Biological Function”, are based on presentations at the ABZ2021 meeting that was held virtually on 19 May 2021 and provide evidence for several biological functions of these structures. The first of its kind, this international conference gathered over 200 scientists from many disciplines to specifically address progress in research involving Z-DNA and Z-RNA. These high-energy left-handed conformers of B-DNA and A-RNA are associated with biological functions and disease outcomes, as evidenced from both mouse and human genetic studies. These alternative structures, referred to as “flipons”, form under physiological conditions, regulate type I interferon responses and induce necroptosis during viral infection. They can also stimulate genetic instability, resulting in adaptive evolution and diseases such as cancer. The meeting featured cutting-edge science that was, for the most part, unpublished. We plan for the ABZ meeting to reconvene in 2022.

Highlights

The biological role of alternative nucleic acid structures has been controversial, especially for Z-DNA
Cell biologists focused on Z-DNA as a cause of genomic instability leading to cancer [4]
We were pleased by the surprise expressed by many in the field about how much they were previously unaware of, even though many have been working on one aspect or another of Z-DNA and Z-RNA for many years

Summary

Introduction

The biological role of alternative nucleic acid structures has been controversial, especially for Z-DNA. Human Mendelian genetic studies of Zα variants proved unambiguously that the Z-conformation was essential to the negative regulation of type I interferon responses [7], while the Zα sensed Z-RNA to induce the programmed cell death pathway called necroptosis during influenza infection [8] These advances were informed by biochemical, biophysical and structural approaches that established the conditions and base modifications necessary to flip from the right- to left-handed conformation under physiological conditions [9]. Computational analyses established that the localization of the repeats that form Z-DNA is not random [10], consistent with its selection for or against particular outcomes This inaugural ABZ meeting (https://abz2021.bio, accessed 16 July 2021) was convened to bring together the leading researchers within the different disciplines that study the Z-conformation, with an intent to celebrate and collaborate.

Meeting Summary

Conclusions

Future Directions