RNA packing specificity and folding during assembly of the bacteriophage MS2
type: Item
instance of: scholarly article
title: RNA packing specificity and folding during assembly of the bacteriophage MS2
zbMATH Open document ID: 1154.92019
DOI: 10.1080/17486700802168445
author: Ottar Rolfsson
author: Katerina Toropova
author: Victoria Morton
author: Simona Francese
author: Gabriella Basnak
author: Gary S. Thompson
author: Stephen W. Homans
author: Alison E. Ashcroft
author: Nicola J. Stonehouse
author: Neil A. Ranson
author: Peter G. Stockley
published in: Computational \& Mathematical Methods in Medicine
publication date: 2009-02-18T00:00:00Z
full work available at URL: https://eudml.org/doc/222986
review text: Summary: Using a combination of biochemistry, mass spectrometry, NMR spectroscopy and cryo-electron microscopy (cryo-EM), we have been able to show that quasi-equivalent conformer switching in the coat protein (CP) of an RNA bacteriophage (MS2) is controlled by a sequence-specific RNA-protein interaction. The RNA component of this complex is an RNA stem-loop encompassing just 19 nts from the phage genomic RNA, which is 3569 nts in length. This binding results in the conversion of a CP dimer from a symmetrical conformation to an asymmetric one. Only when both symmetrical and asymmetrical dimers are present in solution is assembly of the \(T = 3\) phage capsid efficient. This implies that the conformers we have characterized by NMR correspond to the two distinct quasi-equivalent conformers seen in the 3D structure of the virion. An icosahedrally-averaged single particle cryo-EM reconstruction of the wild-type phage (to \(\sim 9\) Å resolution) has revealed icosahedrally ordered density encompassing up to 90\% of the single-stranded RNA genome. The RNA is seen with a novel arrangement of two concentric shells, with connections between them along the 5-fold symmetry axes. RNA in the outer shell interacts with each of the 90 CP dimers in the \(T = 3\) capsid and although the density is icosahedrally averaged, there appears to be a different average contact at the different quasi-equivalent protein dimers: precisely the result that would be expected if protein conformer switching is RNA-mediated throughout the assembly pathway. This unprecedented RNA structure provides new constraints for models of viral assembly and we describe experiments aimed at probing these. Together, these results suggest that viral genomic RNA folding is an important factor in efficient assembly, and further suggest that RNAs that could sequester viral CPs but not fold appropriately could act as potent inhibitors of viral assembly.
Mathematics Subject Classification ID: 92C40
zbMATH DE Number: 5508962
zbMATH Keywords: RNA-protein interactions
zbMATH Keywords: MS2
zbMATH Keywords: ssRNA virus
zbMATH Keywords: genomic RNA structure and folding
zbMATH Keywords: cryo-electron microscopy
zbMATH Keywords: viral assembly
MaRDI profile type: Publication
OpenAlex ID: W2107483791
Wikidata QID: Q61832140
description: scientific article; zbMATH DE number 5508962