Intensive Distribution of G₂-Quaduplexes in the Pseudorabies Virus Genome and Their Sensitivity to Cations and G-Quadruplex Ligands.

Hui Deng,Dengguo Wei,Huan Zhou,Zhen Li,Zhiquan Yang,Xiaohui Niu,Yashu Zhang,Sisi Liu,Bowen Gong

doi:10.3390/molecules24040774

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https://doi.org/10.3390/molecules24040774

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Abstract

Guanine-rich sequences in the genomes of herpesviruses can fold into G-quadruplexes. Compared with the widely-studied G3-quadruplexes, the dynamic G2-quadruplexes are more sensitive to the cell microenvironment, but they attract less attention. Pseudorabies virus (PRV) is the model species for the study of the latency and reactivation of herpesvirus in the nervous system. A total of 1722 G2-PQSs and 205 G3-PQSs without overlap were identified in the PRV genome. Twelve G2-PQSs from the CDS region exhibited high conservation in the genomes of the Varicellovirus genus. Eleven G2-PQSs were 100% conserved in the repeated region of the annotated PRV genomes. There were 212 non-redundant G2-PQSs in the 3′ UTR and 19 non-redundant G2-PQSs in the 5′ UTR, which would mediate gene expression in the post-transcription and translation processes. The majority of examined G2-PQSs formed parallel structures and exhibited different sensitivities to cations and small molecules in vitro. Two G2-PQSs, respectively, from 3′ UTR of UL5 (encoding helicase motif) and UL9 (encoding sequence-specific ori-binding protein) exhibited diverse regulatory activities with/without specific ligands in vivo. The G-quadruplex ligand, NMM, exhibited a potential for reducing the virulence of the PRV Ea strain. The systematic analysis of the distribution of G2-PQSs in the PRV genomes could guide further studies of the G-quadruplexes’ functions in the life cycle of herpesviruses.

Highlights

The life-long latency of herpesviruses poses potential threats to the host at any time, and the reason for the wide existence of the GC-rich sequences in herpesvirus genomes remains unknown [1].Guanine-rich sequences have been discovered to form special DNA or RNA secondary structures calledG-quadruplexes
The formation of a G-quadruplex in the 3’ end untranslated regions (30 untranslated region (UTR)) was reported to result in gene expression decrease, The formation of a G-quadruplex in the 3′ UTR was reported to result in gene expression alternative polyadenylation [39], and retrotransposition [40].This study found that there were more decrease, alternative polyadenylation [39], and retrotransposition [40].This study found that there were more G2-putative G-quadruplex sequences (PQS) in the 3′ UTR than in the 5′ UTR, in Pseudorabies virus (PRV) (Table 1)
The systematic analysis of the distribution of G2 -PQS in the PRV genomes provides a clear guide for elaborated studies of their functions, related to the establishment of latency and its reactivation in herpesviruses

Summary

Introduction

Guanine-rich sequences have been discovered to form special DNA or RNA secondary structures called. They are composed of π-stacked G-quartets via hydrogen-bonded structure in DNA or RNA [2]. Each G-quartet contains four guanines held by eight hydrogen bonds, and coordinated with a central monovalent cation, such as K+ and Na+. The G3 -putative quadruplex sequences (G3 -PQSs) in the form of (G3+ N1-7 ) G3+ form three or more G-quartets in the structures (Figure 1), and they exhibited. Molecules 2019, 24, 774 sequences (G3-PQSs) in the form of (G3+N1-7)3G3+ form three or more G-quartets in the structures 1), andstability they exhibited good thermal stability under near-physiological conditions [3]. The good thermal under near-physiological conditions [3]

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