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Sequestering the 5′‐cap for viral RNA packaging

Many viruses evolved mechanisms for capping the 5′‐ends of their plus‐strand RNAs as a means of hijacking the eukaryotic messenger RNA (mRNA) splicing/translation machinery. Although capping is critical for replication, the RNAs of these viruses have other essential functions including their requirement to be packaged as either genomes or pre‐genomes into progeny viruses. Recent studies indicate that human immunodeficiency virus type‐1 (HIV‐1) RNAs are segregated between splicing/translation and packaging functions by a mechanism that involves structural sequestration of the 5′‐cap. Here, we examined studies reported for other viruses and retrotransposons that require both selective packaging of their RNAs and 5′‐RNA capping for host‐mediated translation. Our findings suggest that viruses and retrotransposons have evolved multiple mechanisms to control 5′‐cap accessibility, consistent with the hypothesis that removal or sequestration of the 5′ cap enables packageable RNAs to avoid capture by the cellular RNA processing and translation machinery.