Strukturierte RNAs in Viren (in German)

In this mini-review we discuss the concept of RNA structure conservation in viruses, using exoribonuclease-resistant RNAs from flaviviruses as prominent examples

Published as Strukturierte RNAs in Viren, Biospektrum 2023.

This article is a short review, but it covers a central idea that has become increasingly important across virology: many viral genomes encode structured RNA elements that actively control the infection cycle, alongside their proteins. In flaviviruses, the 3'UTR is a particularly rich example because it contains conserved folds that regulate replication, translation, host adaptation, and immune evasion.

The focus here is on exoribonuclease-resistant RNAs, or xrRNAs. These elements are interesting because they act mechanically, i.e. their three-dimensional fold stalls the cellular XRN1 exoribonuclease and thereby generates subgenomic flaviviral RNAs (sfRNAs). Those sfRNAs are now known to contribute to pathogenicity, host-range effects, and immune modulation in multiple flavivirus groups.

What makes xrRNAs especially attractive from a structural-biology perspective is that they illustrate RNA function in a very direct way. Their activity depends on conserved topology rather than simple sequence identity. That means they are an ideal example of why RNA structure conservation matters in virology: two viral RNAs can diverge substantially at sequence level while preserving a fold that continues to perform the same mechanistic task.

The review therefore works on two levels: at the biological level, it summarizes why structured 3'UTR elements matter for the viral life cycle and how xrRNAs help viruses manipulate host RNA decay pathways. At the conceptual level, it argues that RNA structures should be treated as evolvable functional modules, not just decorative features of untranslated regions. That framing connects this short piece to a much broader body of comparative work on conserved viral RNAs.

Another useful aspect of the article is that it points beyond natural virus biology toward design. If an RNA fold can reliably block an exoribonuclease in nature, then the same principle can potentially be repurposed in synthetic systems. That is where the connection to RNA design and future therapeutic applications comes in. xrRNAs are interesting because they explain flavivirus biology and because they may serve as modular regulatory parts in engineered RNAs.

The same property makes the topic relevant for RNA therapeutics and mRNA technology. Structured RNA elements that control stability or degradation are candidates for engineering transcript lifetime and behavior. Viral xrRNAs cannot simply be copied into therapeutic constructs, but they are a natural, tested design principle for mechanically active RNA control.

The piece bridges comparative viral RNA structure analysis, xrRNA discovery, and later efforts in synthetic and mechanically active RNA design. Even though the article itself is shorter and more magazine-style than a primary research paper, the underlying concept is foundational and deserves more context than a brief teaser. Readers who want to follow that thread into primary research can move from here to Discoveries of Exoribonuclease-Resistant Structures of Insect-Specific Flaviviruses Isolated in Zambia or to Rational design of mechanically active RNAs.

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