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A folded viral noncoding RNA blocks host cell exoribonucleases through a conformationally dynamic RNA structure.

ABSTRACT: Folded RNA elements that block processive 5' ? 3' cellular exoribonucleases (xrRNAs) to produce biologically active viral noncoding RNAs have been discovered in flaviviruses, potentially revealing a new mode of RNA maturation. However, whether this RNA structure-dependent mechanism exists elsewhere and, if so, whether a singular RNA fold is required, have been unclear. Here we demonstrate the existence of authentic RNA structure-dependent xrRNAs in dianthoviruses, plant-infecting viruses unrelated to animal-infecting flaviviruses. These 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 xrRNA by X-ray crystallography, we reveal a complex fold that is very different from that of the flavivirus xrRNAs. However, both versions of xrRNAs contain a unique topological feature, a pseudoknot that creates a protective ring around the 5' end of the RNA structure; this may be a defining structural feature of xrRNAs. Single-molecule FRET experiments reveal that the dianthovirus xrRNAs undergo conformational changes and can use "codegradational 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.

SUBMITTER: Steckelberg AL

PROVIDER: S-EPMC6016793 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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A folded viral noncoding RNA blocks host cell exoribonucleases through a conformationally dynamic RNA structure.

Steckelberg Anna-Lena AL Akiyama Benjamin M BM Costantino David A DA Sit Tim L TL Nix Jay C JC Kieft Jeffrey S JS

Proceedings of the National Academy of Sciences of the United States of America 20180604 25

Folded RNA elements that block processive 5' → 3' cellular exoribonucleases (xrRNAs) to produce biologically active viral noncoding RNAs have been discovered in flaviviruses, potentially revealing a new mode of RNA maturation. However, whether this RNA structure-dependent mechanism exists elsewhere and, if so, whether a singular RNA fold is required, have been unclear. Here we demonstrate the existence of authentic RNA structure-dependent xrRNAs in dianthoviruses, plant-infecting viruses unrelat ...[more]

PMID: 29866852

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A folded viral noncoding RNA blocks host cell exoribonucleases through a conformationally dynamic RNA structure.

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A folded viral noncoding RNA blocks host cell exoribonucleases through a conformationally dynamic RNA structure.

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