Trans-Acting RNA–RNA Interactions in Segmented RNA Viruses

Newburn, Laura R.; White, K. Andrew

doi:10.3390/v11080751

Cited by 16 publications

(11 citation statements)

References 55 publications

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“…Other viruses also have very specific packaging requirements to ensure that they maintain infectivity. In the case of influenza with its linear negative-sense, single-stranded RNA genome, segments minimally base-pair to ensure that they are all packaged into the virion [ 76 ], while with retroviruses, packaging requires formation of a dsRNA dimer from 2 single-stranded, positive-sense, linear RNA molecules [ 77 , 78 ]. The choreography of wrapping these small dsRNA regions in protein could also generate topological stress capable of inducing Z-RNA formation and ZBP1 activation, especially in the RNA tangles formed from defective genomic copies.…”

Section: The Backgroundmentioning

confidence: 99%

To “Z” or not to “Z”: Z-RNA, self-recognition, and the MDA5 helicase

Herbert

2021

PLoS Genet

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Double-stranded RNA (dsRNA) is produced both by virus and host. Its recognition by the melanoma differentiation–associated gene 5 (MDA5) initiates type I interferon responses. How can a host distinguish self-transcripts from nonself to ensure that responses are targeted correctly? Here, I discuss a role for MDA5 helicase in inducing Z-RNA formation by Alu inverted repeat (AIR) elements. These retroelements have highly conserved sequences that favor Z-formation, creating a site for the dsRNA-specific deaminase enzyme ADAR1 to dock. The subsequent editing destabilizes the dsRNA, ending further interaction with MDA5 and terminating innate immune responses directed against self. By enabling self-recognition, Alu retrotransposons, once invaders, now are genetic elements that keep immune responses in check. I also discuss the possible but less characterized roles of the other helicases in modulating innate immune responses, focusing on DExH-box helicase 9 (DHX9) and Mov10 RISC complex RNA helicase (MOV10). DHX9 and MOV10 function differently from MDA5, but still use nucleic acid structure, rather than nucleotide sequence, to define self. Those genetic elements encoding the alternative conformations involved, referred to as flipons, enable helicases to dynamically shape a cell’s repertoire of responses. In the case of MDA5, Alu flipons switch off the dsRNA-dependent responses against self. I suggest a number of genetic systems in which to study interactions between flipons and helicases further.

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Section: The Backgroundmentioning

confidence: 99%

To “Z” or not to “Z”: Z-RNA, self-recognition, and the MDA5 helicase

Herbert

2021

PLoS Genet

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“…None of the known multipartite viruses has adopted this packaging strategy: cases where more than one segments are packaged in the same particle exist, i.e. the RNA3 and RNA4 segments of bromoviruses (59) or RNA1 and RNA2 of dianthoviruses (60,61), but it is always the same segments which are packaged together; the process is not random (62).…”

Section: Multicomponent Viral Systemsmentioning

confidence: 99%

The Curious Strategy of Multipartite Viruses

Michalakis

Blanc

2020

Annu. Rev. Virol.

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Multipartite virus genomes are composed of several segments, each packaged in a distinct viral particle. Although this puzzling genome architecture is found in ∼17% of known viral species, its distribution among hosts or among distinct types of genome-composing nucleic acid remains poorly understood. No convincing advantage of multipartitism has been identified, yet the maintenance of genomic integrity appears problematic. Here we review recent studies shedding light on these issues. Multipartite viruses rapidly modify the copy number of each segment/gene from one host species to another, a putative benefit if host switches are common. One multipartite virus functions in a multicellular way: The segments do not all need to be present in the same cell and can functionally complement across cells, maintaining genome integrity within hosts. The genomic integrity maintenance during host-to-host transmission needs further elucidation. These features challenge several virology foundations and could apply to other multicomponent viral systems.

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“…The concept of RNA–RNA interactions as specifiers of biological choice has emerged as a major factor for many non-coding RNAs, and its understanding underpins many RNA directed events including transcription, splicing, translation, and RNA decay [ 27 , 28 , 29 ]. In other RNA viruses with segmented genomes (e.g., Influenza A virus, Red clover necrotic mosaic virus), trans -acting RNA–RNA interactions have also been found to play an important role in genome packaging [ 30 , 31 ].…”

Section: Rna Complex Formation and Rna Network May Initiate Packagingmentioning

confidence: 99%

RNA Origami: Packaging a Segmented Genome in Orbivirus Assembly and Replication

Sung

Roy

2021

Viruses

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Understanding how viruses with multi-segmented genomes incorporate one copy of each segment into their capsids remains an intriguing question. Here, we review our recent progress and describe the advancements made in understanding the genome packaging mechanism of a model nonenveloped virus, Bluetongue virus (BTV), with a 10-segment (S1–S10) double-strand RNA (dsRNA) genome. BTV (multiple serotypes), a member of the Orbivirus genus in the Reoviridae family, is a notable pathogen for livestock and is responsible for significant economic losses worldwide. This has enabled the creation of an extensive set of reagents and assays, including reverse genetics, cell-free RNA packaging, and bespoke bioinformatics approaches, which can be directed to address the packaging question. Our studies have shown that (i) UTRs enable the conformation of each segment necessary for the next level of RNA–RNA interaction; (ii) a specific order of intersegment interactions leads to a complex RNA network containing all the active components in sorting and packaging; (iii) networked segments are recruited into nascent assembling capsids; and (iv) select capsid proteins might be involved in the packaging process. The key features of genome packaging mechanisms for BTV and related dsRNA viruses are novel and open up new avenues of potential intervention.

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Trans-Acting RNA–RNA Interactions in Segmented RNA Viruses

Cited by 16 publications

References 55 publications

To “Z” or not to “Z”: Z-RNA, self-recognition, and the MDA5 helicase

To “Z” or not to “Z”: Z-RNA, self-recognition, and the MDA5 helicase

The Curious Strategy of Multipartite Viruses

RNA Origami: Packaging a Segmented Genome in Orbivirus Assembly and Replication

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