RNA-mediated capsid nucleation of bacteriophage MS2 coat proteins confers RNA packaging selectivity

Simple viruses, such as bacteriophage MS2, spontaneously assemble into a protein shell encapsulating a single molecule of genomic RNA. Infection of host cells by MS2 results in replication of the RNA and expression of viral coat proteins, which then package the cognate viral RNA with high selectivity despite the presence of competing host RNAs. How the MS2 coat proteins selectively self-assemble around their own RNA is poorly understood. Using interferometric scattering microscopy and quantitative gel electrophoresis, we show that the RNA-mediated nucleation-and-growth assembly pathway of MS2 coat proteins can drive preferential encapsidation of cognate RNA, and hence selective packaging.