4.5 Article

HBV RNA pre-genome encodes specific motifs that mediate interactions with the viral core protein that promote nucleocapsid assembly

期刊

NATURE MICROBIOLOGY
卷 2, 期 8, 页码 -

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/nmicrobiol.2017.98

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资金

  1. UK MRC [MR/N021517/1]
  2. University of Leeds
  3. University of York
  4. Wellcome Trust [089311/Z/09/Z, 090932/Z/09/Z, 106692, 110145, 110146]
  5. Royal Society Leverhulme Trust Senior Research Fellowship [LT130088]
  6. EPSRC grant [EP/K028286/1]
  7. Early Career Leverhulme Trust Fellowship [ECF-2013-019]
  8. National Institutes of Health grant [R01-AI118933]
  9. Engineering and Physical Sciences Research Council [EP/K028286/1, EP/K027689/1] Funding Source: researchfish
  10. Medical Research Council [MR/N021517/1] Funding Source: researchfish
  11. Wellcome Trust [089311/Z/09/Z] Funding Source: Wellcome Trust
  12. EPSRC [EP/K028286/1, EP/K027689/1] Funding Source: UKRI
  13. MRC [MR/N021517/1] Funding Source: UKRI
  14. Royal Society [LT130088] Funding Source: Royal Society

向作者/读者索取更多资源

Formation of the hepatitis B virus nucleocapsid is an essential step in the viral lifecycle, but its assembly is not fully understood. We report the discovery of sequence-specific interactions between the viral pre-genome and the hepatitis B core protein that play roles in defining the nucleocapsid assembly pathway. Using RNA SELEX and bioinformatics, we identified multiple regions in the pre-genomic RNA with high affinity for core protein dimers. These RNAs form stem-loops with a conserved loop motif that trigger sequence-specific 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-electron microscopy reconstruction of the T = 4 VLPs assembled in the presence of one of the RNAs reveals a unique internal feature connected to the main core protein 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 core protein. These core protein-RNA contacts may play one or more roles in regulating the organization of the pre-genome during nucleocapsid assembly, facilitating subsequent reverse transcription and acting as a nucleation complex for nucleocapsid assembly.

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