Compositional complementarity between genomic RNA and coat proteins in positive-sense single-stranded RNA viruses

Marlene Adlhart, Florian Poetsch, Mario Hlevnjak, Megan Hoogmoed, Anton A. Polyansky, Bojan Zagrovic (Corresponding author)

Publications: Contribution to journalArticlePeer Reviewed

Abstract

During packaging in positive-sense single-stranded RNA (+ssRNA) viruses, coat proteins (CPs) interact directly with multiple regions in genomic RNA (gRNA), but the underlying physicochemical principles remain unclear. Here we analyze the high-resolution cryo-EM structure of bacteriophage MS2 and show that the gRNA/CP binding sites, including the known packaging signal, overlap significantly with regions where gRNA nucleobase-density profiles match the corresponding CP nucleobase-affinity profiles. Moreover, we show that the MS2 packaging signal corresponds to the global minimum in gRNA/CP interaction energy in the unstructured state as derived using a linearly additive model and knowledge-based nucleobase/amino-acid affinities. Motivated by this, we predict gRNA/CP interaction sites for a comprehensive set of 1082 +ssRNA viruses. We validate our predictions by comparing them with site-resolved information on gRNA/CP interactions derived in SELEX and CLIP experiments for 10 different viruses. Finally, we show that in experimentally studied systems CPs frequently interact with autologous coding regions in gRNA, in agreement with both predicted interaction energies and a recent proposal that proteins in general tend to interact with own mRNAs, if unstructured. Our results define a self-consistent framework for understanding packaging in +ssRNA viruses and implicate interactions between unstructured gRNA and CPs in the process.

Original languageEnglish
Pages (from-to)4054-4067
Number of pages14
JournalNucleic Acids Research
Volume50
Issue number7
DOIs
Publication statusPublished - 22 Apr 2022

Austrian Fields of Science 2012

  • 106023 Molecular biology

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