Diallo, M. A. et al. (2023) A fish herpesvirus highlights functional diversities among Zα domains related to phase separation induction and A-to-Z conversion. Nucleic Acids Research, 51(2), pp. 806-830. (doi: 10.1093/nar/gkac761) (PMID:36130731) (PMCID:PMC9881149)
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Abstract
Zalpha (Zα) domains bind to left-handed Z-DNA and Z-RNA. The Zα domain protein family includes cellular (ADAR1, ZBP1 and PKZ) and viral (vaccinia virus E3 and cyprinid herpesvirus 3 (CyHV-3) ORF112) proteins. We studied CyHV-3 ORF112, which contains an intrinsically disordered region and a Zα domain. Genome editing of CyHV-3 indicated that the expression of only the Zα domain of ORF112 was sufficient for normal viral replication in cell culture and virulence in carp. In contrast, its deletion was lethal for the virus. These observations revealed the potential of the CyHV-3 model as a unique platform to compare the exchangeability of Zα domains expressed alone in living cells. Attempts to rescue the ORF112 deletion by a broad spectrum of cellular, viral, and artificial Zα domains showed that only those expressing Z-binding activity, the capacity to induce liquid-liquid phase separation (LLPS), and A-to-Z conversion, could rescue viral replication. For the first time, this study reports the ability of some Zα domains to induce LLPS and supports the biological relevance of dsRNA A-to-Z conversion mediated by Zα domains. This study expands the functional diversity of Zα domains and stimulates new hypotheses concerning the mechanisms of action of proteins containing Zα domains.
| Item Type: | Articles |
|---|---|
| Additional Information: | University of Liège [ARC15/19-12 to A.V.]; Fonds National Belge de la Recherche Scientifique (FNRS) [CDR J.0094.15 and PDR T.0241.19 to A.V.]; Welbio [WELBIO-CR-2022 A-14 12 to A.V.]; Walloon Region [ERANets NucNanoFish 2010052 to A.V.]; Medical Research Council [MC_UU_12014/3 to A.J.D.]; Vrije Universiteit Brussel [Spearhead grant SRP51 to P.T.]; European Commission [EC H2020-WIDESPREAD-2020-5 Twinning grant PhasAge, 952334, and EC H2020-MSCA-RISE Action grant IDPfun 778247 to P.T.]; Japan Society for the promotion of science Kakenhi [21H02081 to Y.X.]. Funding for open access charge: University of Liège (Belgium). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Suarez, Dr Nicolas and Davison, Professor Andrew |
| Authors: | Diallo, M. A., Pirotte, S., Hu, Y., Morvan, L., Rakus, K., Suárez, N. M., PoTsang, L., Saneyoshi, H., Xu, Y., Davison, A. J., Tompa, P., Sussman, J. L., and Vanderplasschen, A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Nucleic Acids Research |
| Publisher: | Oxford University Press |
| ISSN: | 0305-1048 |
| ISSN (Online): | 1362-4962 |
| Published Online: | 22 September 2022 |
| Copyright Holders: | Copyright © 2022 The Authors |
| First Published: | First published in Nucleic Acids Research 51(2): 806-830 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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