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Updated: May 17, 2026
12:20
Bacterial Artificial Chromosomes: A Functional Genomics Tool for the Study of Positive-strand RNA Viruses
Published on: December 29, 2015
Phleboviruses encapsidate their genomes by sequestering RNA bases.
Donald D Raymond1, Mary E Piper, Sonja R Gerrard
1Life Sciences Institute, Department of Biological Chemistry, Cell and Molecular Biology Program, University of Michigan, Ann Arbor, MI 48109, USA.
Summary
Rift Valley fever and Toscana viruses lack treatments. Researchers determined the high-resolution structure of their nucleocapsid protein (N) bound to RNA, revealing a common building block for viral ribonucleoprotein complexes.
Area of Science:
- Structural biology
- Virology
- Molecular biology
Background:
- Rift Valley fever and Toscana viruses are significant human pathogens.
- Effective therapeutics for these phleboviruses are currently unavailable.
- Phleboviruses possess segmented negative-sense RNA genomes packaged into ribonucleoprotein (RNP) complexes.
Purpose of the Study:
- To elucidate the high-resolution structure of phlebovirus nucleocapsid protein (N)-RNA complexes.
- To understand the structural basis of the irregular and asymmetric RNP architecture.
- To identify potential targets for antiviral drug development.
Main Methods:
- Reconstitution of Rift Valley fever virus N-RNA complexes using defined RNA lengths.
- Determination of crystal structures of N-RNA complexes.
- Analysis of N-N subunit contacts and RNA binding interfaces.
Main Results:
- Crystal structures revealed tetrameric, pentameric, and hexameric N-RNA multimers.
- A highly flexible alpha-helical arm mediates N-N subunit contacts and RNP asymmetry.
- An invariant monomeric RNP building block, comprising N core, neighboring N arm, and four RNA nucleotides, was identified.
- RNA bases are sequestered in a hydrophobic slot, incompatible with base pairing or polymerase recognition.
Conclusions:
- The study defines the fundamental monomeric building block of phlebovirus RNPs.
- The structural findings explain the irregular RNP architecture and provide insights into genome packaging.
- The incompatible RNA base interactions suggest a mechanism for genome replication regulation.
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