Self-Assembly of Measles Virus Nucleocapsid-like Particles: Kinetics and RNA Sequence Dependence

Angew Chem Int Ed Engl. 2016 Aug 1;55(32):9356-60. doi: 10.1002/anie.201602619. Epub 2016 Jun 6.


Measles virus RNA genomes are packaged into helical nucleocapsids (NCs), comprising thousands of nucleo-proteins (N) that bind the entire genome. N-RNA provides the template for replication and transcription by the viral polymerase and is a promising target for viral inhibition. Elucidation of mechanisms regulating this process has been severely hampered by the inability to controllably assemble NCs. Here, we demonstrate self-organization of N into NC-like particles in vitro upon addition of RNA, providing a simple and versatile tool for investigating assembly. Real-time NMR and fluorescence spectroscopy reveals biphasic assembly kinetics. Remarkably, assembly depends strongly on the RNA-sequence, with the genomic 5' end and poly-Adenine sequences assembling efficiently, while sequences such as poly-Uracil are incompetent for NC formation. This observation has important consequences for understanding the assembly process.

Keywords: NMR spectroscopy; fluorescence spectroscopy; measles; nucleocapsids; self-assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Kinetics
  • Measles virus / metabolism*
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleocapsid / chemistry
  • Nucleocapsid / metabolism*
  • Nucleocapsid Proteins
  • Nucleoproteins / chemistry
  • Nucleoproteins / metabolism*
  • RNA, Viral / chemistry
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*
  • Spectrometry, Fluorescence
  • Viral Proteins / chemistry
  • Viral Proteins / metabolism*
  • Virus Assembly*


  • Nucleocapsid Proteins
  • Nucleoproteins
  • RNA, Viral
  • Viral Proteins
  • nucleoprotein, Measles virus