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bioRxiv · 10.1101/262683

A folded viral noncoding RNA blocks host cell exoribonucleases through programmed remodeling of RNA structure

Steckelberg, A.-L.·Akiyama, B. M.·Costantino, D. A.·Sit, T. L.·Nix, J. C.·Kieft, J. S.
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Abstract

Folded RNA elements that block processive 5'[->]3' cellular exoribonucleases (xrRNAs) to produce biologically active viral non-coding RNAs were discovered in flaviviruses, potentially revealing a new mode of RNA maturation. However, it was unknown if this RNA structure-dependent mechanism exists elsewhere and if so, whether a singular RNA fold is required. Here, we demonstrate the existence of authentic RNA structure-dependent xrRNAs in dianthoviruses, plant-infecting viruses unrelated to animal-infecting flaviviruses. These novel xrRNAs have no sequence similarity to known xrRNAs, thus we used a combination of biochemistry and virology to characterize their sequence requirements and mechanism of stopping exoribonucleases. By solving the structure of a dianthovirus xrRNAs by x-ray crystallography, we reveal a complex fold that is very different from the flavivirus xrRNAs. However, both versions of xrRNAs contain a unique topological feature that is created by a different set of intramolecular contacts; this may be a defining structural feature of xrRNAs. Remarkably, the dianthovirus xrRNA can use co-degradational remodeling, exploiting the exoribonucleases degradation-linked helicase activity to help form their resistant structure; such a mechanism has not previously been reported. Convergent evolution has created RNA structure-dependent exoribonuclease resistance in different contexts, which establishes it as a general RNA maturation mechanism and defines xrRNAs as an authentic functional class of RNAs.

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Steckelberg, A.-L., Akiyama, B. M., Costantino, D. A., Sit, T. L., Nix, J. C., Kieft, J. S.. 2018-02-09. A folded viral noncoding RNA blocks host cell exoribonucleases through programmed remodeling of RNA structure. https://doi.org/10.1101/262683

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