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Frustration and fidelity in influenza genome assembly
The genome of the influenza virus consists of eight distinct single-stranded RNA segments, each encoding proteins essential for the viral life cycle. When the virus infects a host cell, these segments must be replicated and packaged into new budding virions. The viral genome is assembled with remark...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893499/ https://www.ncbi.nlm.nih.gov/pubmed/31690232 http://dx.doi.org/10.1098/rsif.2019.0411 |
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author | Farheen, Nida Thattai, Mukund |
author_facet | Farheen, Nida Thattai, Mukund |
author_sort | Farheen, Nida |
collection | PubMed |
description | The genome of the influenza virus consists of eight distinct single-stranded RNA segments, each encoding proteins essential for the viral life cycle. When the virus infects a host cell, these segments must be replicated and packaged into new budding virions. The viral genome is assembled with remarkably high fidelity: experiments reveal that most virions contain precisely one copy of each of the eight RNA segments. Cell-biological studies suggest that genome assembly is mediated by specific reversible and irreversible interactions between the RNA segments and their associated proteins. However, the precise inter-segment interaction network remains unresolved. Here, we computationally predict that tree-like irreversible interaction networks guarantee high-fidelity genome assembly, while cyclic interaction networks lead to futile or frustrated off-pathway products. We test our prediction against multiple experimental datasets. We find that tree-like networks capture the nearest-neighbour statistics of RNA segments in packaged virions, as observed by electron tomography. Just eight tree-like networks (of a possible 262 144) optimally capture both the nearest-neighbour data and independently measured RNA–RNA binding and co-localization propensities. These eight do not include the previously proposed hub-and-spoke and linear networks. Rather, each predicted network combines hub-like and linear features, consistent with evolutionary models of interaction gain and loss. |
format | Online Article Text |
id | pubmed-6893499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-68934992019-12-09 Frustration and fidelity in influenza genome assembly Farheen, Nida Thattai, Mukund J R Soc Interface Life Sciences–Physics interface The genome of the influenza virus consists of eight distinct single-stranded RNA segments, each encoding proteins essential for the viral life cycle. When the virus infects a host cell, these segments must be replicated and packaged into new budding virions. The viral genome is assembled with remarkably high fidelity: experiments reveal that most virions contain precisely one copy of each of the eight RNA segments. Cell-biological studies suggest that genome assembly is mediated by specific reversible and irreversible interactions between the RNA segments and their associated proteins. However, the precise inter-segment interaction network remains unresolved. Here, we computationally predict that tree-like irreversible interaction networks guarantee high-fidelity genome assembly, while cyclic interaction networks lead to futile or frustrated off-pathway products. We test our prediction against multiple experimental datasets. We find that tree-like networks capture the nearest-neighbour statistics of RNA segments in packaged virions, as observed by electron tomography. Just eight tree-like networks (of a possible 262 144) optimally capture both the nearest-neighbour data and independently measured RNA–RNA binding and co-localization propensities. These eight do not include the previously proposed hub-and-spoke and linear networks. Rather, each predicted network combines hub-like and linear features, consistent with evolutionary models of interaction gain and loss. The Royal Society 2019-11 2019-11-06 /pmc/articles/PMC6893499/ /pubmed/31690232 http://dx.doi.org/10.1098/rsif.2019.0411 Text en © 2019 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Life Sciences–Physics interface Farheen, Nida Thattai, Mukund Frustration and fidelity in influenza genome assembly |
title | Frustration and fidelity in influenza genome assembly |
title_full | Frustration and fidelity in influenza genome assembly |
title_fullStr | Frustration and fidelity in influenza genome assembly |
title_full_unstemmed | Frustration and fidelity in influenza genome assembly |
title_short | Frustration and fidelity in influenza genome assembly |
title_sort | frustration and fidelity in influenza genome assembly |
topic | Life Sciences–Physics interface |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893499/ https://www.ncbi.nlm.nih.gov/pubmed/31690232 http://dx.doi.org/10.1098/rsif.2019.0411 |
work_keys_str_mv | AT farheennida frustrationandfidelityininfluenzagenomeassembly AT thattaimukund frustrationandfidelityininfluenzagenomeassembly |