A folded viral noncoding RNA blocks host cell exoribonucleases through a conformationally dynamic RNA structure
| Autor: | Anna-Lena Steckelberg, Benjamin M. Akiyama, Jeffrey S. Kieft, David A. Costantino, Jay C. Nix, Tim L. Sit |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
RNA Folding RNA Stability Computational biology 03 medical and health sciences Exoribonuclease Animals Nucleic acid structure 3' Untranslated Regions Multidisciplinary Base Sequence 030102 biochemistry & molecular biology biology Chemistry Flavivirus RNA Single-molecule FRET Biological Sciences biology.organism_classification Non-coding RNA Dianthovirus Exoribonucleases 030104 developmental biology Host-Pathogen Interactions Nucleic Acid Conformation RNA Viral Pseudoknot |
| Zdroj: | Proceedings of the National Academy of Sciences. 115:6404-6409 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1802429115 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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