Patel, N orcid.org/0000-0001-6098-3633, White, SJ orcid.org/0000-0002-9227-9461, Thompson, RF et al. (9 more authors) (2017) HBV RNA pre-genome encodes specific motifs that mediate interactions with the viral core protein that promote nucleocapsid assembly. Nature Microbiology, 2 (8). 17098. ISSN 2058-5276
Abstract
Formation of the Hepatitis B (HBV) nucleocapsid (NC) is an essential step in the viral lifecycle but its assembly is not fully understood. We report the discovery of sequencespecific interactions between the viral pre-genome and HBV core protein (Cp) that play roles in defining the NC assembly pathway. Using RNA SELEX and bioinformatics we identified multiple regions in the pre-genomic RNA with high-affinity for Cp dimers.
These RNAs form stem-loops with a conserved loop motif that trigger sequencespecific
assembly of virus-like particles (VLPs) at much higher fidelity and yield than in the absence of RNA. The RNA oligos do not interact with preformed RNA-free VLPs, so their effects must occur during particle assembly. Asymmetric cryo-EM reconstruction of the T=4 VLPs assembled in the presence of one of the RNAs reveals a unique internal
feature connected to the main Cp shell via lobes of density. Biophysical assays suggest that this is a complex involving several RNA oligos interacting with the C-terminal arginine-rich domains of Cp. These Cp-RNA contacts may play a role(s) in regulating the organization of the pre-genome during nucleocapsid assembly, facilitating subsequent reverse transcription and acting as a nucleation complex for NC assembly.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2017 Author(s). This is an author produced version of a paper published in Nature Microbiology. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Biological Chemistry (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Cryo EM, Image Processing (Leeds) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MR/N021517/1 Wellcome Trust 090932/Z/09/Z |
Depositing User: | Symplectic Publications |
Date Deposited: | 24 May 2017 09:58 |
Last Modified: | 06 Oct 2020 13:55 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/nmicrobiol.2017.98 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:116755 |