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Self‐Assembly of Measles Virus Nucleocapsid‐like Particles: Kinetics and RNA Sequence Dependence
Author(s) -
Milles Sigrid,
Jensen Malene Ringkjøbing,
Communie Guillaume,
Maurin Damien,
Schoehn Guy,
Ruigrok Rob W. H.,
Blackledge Martin
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201602619
Subject(s) - rna , measles virus , uracil , transcription (linguistics) , biology , genome , sequence (biology) , polymerase , kinetics , rna polymerase , chemistry , computational biology , virology , biophysics , genetics , dna , gene , measles , physics , linguistics , philosophy , vaccination , quantum mechanics
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.