tetano
Editor, Senior Moderator
J R Soc Interface. 2019 Nov 29;16(160):20190411. doi: 10.1098/rsif.2019.0411. Epub 2019 Nov 6. [h=1]Frustration and fidelity in influenza genome assembly.[/h]
Farheen N[SUP]1[/SUP], Thattai M[SUP]2[/SUP].
[h=3]Author information[/h] 1 Indian Institute of Science Education and Research, Pune 411008, India. 2 Simons Centre for the Study of Living Machines, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] influenza; network evolution; segmented virus; self-assembly
PMID: 31690232 DOI: 10.1098/rsif.2019.0411
Farheen N[SUP]1[/SUP], Thattai M[SUP]2[/SUP].
[h=3]Author information[/h] 1 Indian Institute of Science Education and Research, Pune 411008, India. 2 Simons Centre for the Study of Living Machines, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] influenza; network evolution; segmented virus; self-assembly
PMID: 31690232 DOI: 10.1098/rsif.2019.0411