RNA Structures and Their Role in Selective Genome Packaging

Ye, Liqing; Ambi, Uddhav B; Olguin-Nava, Marco; Gribling-Burrer, Anne-Sophie; Ahmad, Shazeb; Bohn, Patrick; Weber, Melanie; Smyth, Redmond P.

doi:10.3390/v13091788

Cited by 9 publications

(5 citation statements)

References 215 publications

(346 reference statements)

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“…Independent research has shown that vRNAs in virio form unique and complex inter-and intra-segmental interaction networks [ 18 , 34 ]. It was confirmed that specific regions within the vRNA (called packaging signals) are crucial for vRNP-vRNP interactions, influencing, among other factors, the appropriate assembly and packaging of all vRNPs set into the nascent virion [ 19 , 21 ]. The RNA secondary structure of the packaging signals plays a key factor in maintaining the virulency of the influenza virus, and their disruption affects viral fitness [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

In vivo secondary structural analysis of Influenza A virus genomic RNA

Szutkowska

Woźniak

Lorent

et al. 2023

Cell. Mol. Life Sci.

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Influenza A virus (IAV) is a respiratory virus that causes epidemics and pandemics. Knowledge of IAV RNA secondary structure in vivo is crucial for a better understanding of virus biology. Moreover, it is a fundament for the development of new RNA-targeting antivirals. Chemical RNA mapping using selective 2’-hydroxyl acylation analyzed by primer extension (SHAPE) coupled with Mutational Profiling (MaP) allows for the thorough examination of secondary structures in low-abundance RNAs in their biological context. So far, the method has been used for analyzing the RNA secondary structures of several viruses including SARS-CoV-2 in virio and in cellulo. Here, we used SHAPE-MaP and dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) for genome-wide secondary structure analysis of viral RNA (vRNA) of the pandemic influenza A/California/04/2009 (H1N1) strain in both in virio and in cellulo environments. Experimental data allowed the prediction of the secondary structures of all eight vRNA segments in virio and, for the first time, the structures of vRNA5, 7, and 8 in cellulo. We conducted a comprehensive structural analysis of the proposed vRNA structures to reveal the motifs predicted with the highest accuracy. We also performed a base-pairs conservation analysis of the predicted vRNA structures and revealed many highly conserved vRNA motifs among the IAVs. The structural motifs presented herein are potential candidates for new IAV antiviral strategies.

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Section: Discussionmentioning

confidence: 99%

In vivo secondary structural analysis of Influenza A virus genomic RNA

Szutkowska

Woźniak

Lorent

et al. 2023

Cell. Mol. Life Sci.

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“…RNA viruses cause serious diseases in crops, leading to significant reductions in annual yields worldwide. Innovative and state-of-the-art strategies are very much required to control/combat with plant viruses in order to meet the demands of the population growth worldwide ( Hill et al, 2021 ; Ye et al, 2021 ). Among several advances in viral control measures, aiming for the steps of the viral assembly process has the potential to save crops from such destructive diseases ( Burroughs et al, 2007 ; Dai et al, 2021 ; Kumar et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

The curious case of genome packaging and assembly in RNA viruses infecting plants

et al. 2023

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Genome packaging is the crucial step for maturation of plant viruses containing an RNA genome. Viruses exhibit a remarkable degree of packaging specificity, despite the probability of co-packaging cellular RNAs. Three different types of viral genome packaging systems are reported so far. The recently upgraded type I genome packaging system involves nucleation and encapsidation of RNA genomes in an energy-dependent manner, which have been observed in most of the plant RNA viruses with a smaller genome size, while type II and III packaging systems, majorly discovered in bacteriophages and large eukaryotic DNA viruses, involve genome translocation and packaging inside the prohead in an energy-dependent manner, i.e., utilizing ATP. Although ATP is essential for all three packaging systems, each machinery system employs a unique mode of ATP hydrolysis and genome packaging mechanism. Plant RNA viruses are serious threats to agricultural and horticultural crops and account for huge economic losses. Developing control strategies against plant RNA viruses requires a deep understanding of their genome assembly and packaging mechanism. On the basis of our previous studies and meticulously planned experiments, we have revealed their molecular mechanisms and proposed a hypothetical model for the type I packaging system with an emphasis on smaller plant RNA viruses. Here, in this review, we apprise researchers the technical breakthroughs that have facilitated the dissection of genome packaging and virion assembly processes in plant RNA viruses.

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“…It is in this latter function that * anze.bozic@ijs.si hairpin motifs can often be found in many positive-strand ssRNA (+ssRNA) viruses, where they serve as packaging signals (PSs). The PS motifs are high-affinity binding sites for the viral capsid (or nucleocapsid) proteins [18,19] that distinguish the viral gRNA from cellular RNAs and drive the virion assembly process. What is more, the emergence of a robust RNA hairpin packaging cassette, analogous to the PSs found in viral gRNAs, has also been observed in the course of laboratory evolution of a bacterial enzyme to package into an artificial nucleocapsid containing its own mRNA [20].…”

Section: Introductionmentioning

confidence: 99%

Context-dependent structure formation of RNA hairpin motifs

Bukina,

Božič

2024

Preprint

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Many functions of ribonucleic acid (RNA) rely on its ability to assume specific sequence-structure motifs. Packaging signals of some RNA viruses - hairpin motifs that interact with capsid proteins and drive self-assembly - are a prominent example. While interaction specificity demands the formation of stable motifs, they remain a small part of a much larger genomic RNA. An underexplored question is how the presence and composition of a flanking sequence around a motif interacts and interferes with its structure. Combining secondary and tertiary structure prediction, we study structural stability of 14 hairpin motifs from the RNA genome of MS2 bacteriophage and show that while some motif structures can be stable in any context, others require specific context provided by the genome. Our results demonstrate how important it is to consider RNA structure in its context and that changes in the flanking sequence of an RNA motif sometimes lead to drastic changes in its structure.

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RNA Structures and Their Role in Selective Genome Packaging

Cited by 9 publications

References 215 publications

In vivo secondary structural analysis of Influenza A virus genomic RNA

In vivo secondary structural analysis of Influenza A virus genomic RNA

The curious case of genome packaging and assembly in RNA viruses infecting plants

Context-dependent structure formation of RNA hairpin motifs

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