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Assays for the Specific Growth Rate and Cell-binding Ability of Rotavirus
Published on: January 28, 2019
Rotavirus RNAs sponge host cell RNA binding proteins and interfere with their subcellular localization
Alfonso Oceguera1, Andrea V Peralta1, Gustavo Martínez-Delgado1
1Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, Mexico.
Abstract:
Cellular mRNAs cycle between translating and non-translating pools, polysomes compose the translating pool, while RNA granules contain translationally-silenced mRNAs, where the RNAs are either stored in stress granules, or accumulate in processing bodies (PBs) or GW-bodies, which have an important role in RNA degradation. Viruses have developed measures to prevent the deleterious effects of these structures during their replication. Rotavirus, the most common agent of viral gastroenteritis, is capable of establishing a successful infection by counteracting several of the antiviral responses of its host. Here, we describe that in rotavirus-infected cells the distribution of several RNA binding proteins is changed causing the disaggregation of PBs, the relocalization of GW-body proteins, and the cytoplasmic accumulation of HuR, a predominantly nuclear protein. We show that this redistribution of proteins is more likely caused by the accumulation of viral RNA in the cytoplasm of infected-cells, where it might be acting as an RBP sponge.
Insights
Rotavirus infection disrupts cellular RNA processing by causing RNA-binding proteins to relocate, disaggregate processing bodies (PBs), and accumulate in the cytoplasm. Viral RNA accumulation likely drives these changes, aiding viral replication.
Area of Science:
- Cellular biology
- Virology
- Molecular biology
Background:
- Cellular mRNAs are dynamically regulated, cycling between translation and silencing in structures like processing bodies (PBs) and GW-bodies.
- Viruses often manipulate host cell machinery, including RNA-protein complexes, to facilitate their replication.
- Rotavirus, a common cause of gastroenteritis, employs strategies to overcome host antiviral defenses.
Purpose of the Study:
- To investigate how rotavirus infection alters the distribution of RNA-binding proteins and RNA granules in host cells.
- To elucidate the mechanisms by which rotavirus counteracts cellular RNA silencing pathways.
Main Methods:
- Analysis of RNA-binding protein distribution in rotavirus-infected cells.
- Microscopy to observe the structural changes in processing bodies (PBs) and GW-bodies.
- Investigating the role of viral RNA accumulation in protein redistribution.
Main Results:
- Rotavirus infection induced the disaggregation of PBs and relocalization of GW-body proteins.
- The predominantly nuclear protein HuR accumulated in the cytoplasm of infected cells.
- Viral RNA accumulation in the cytoplasm is proposed as a mechanism to sequester RNA-binding proteins (RBPs).
Conclusions:
- Rotavirus infection significantly remodels host cell RNA granules and protein localization.
- Viral RNA acts as a potential 'RBP sponge,' sequestering host factors to promote viral replication.
- These viral strategies contribute to successful rotavirus infection by evading host antiviral responses.
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