6D3P

Crystal structure of an exoribonuclease-resistant RNA from Sweet clover necrotic mosaic virus (SCNMV)

Summary for 6D3P

• Entry DOI: 10.2210/pdb6d3p/pdb
• Descriptor: RNA (45-MER), IRIDIUM HEXAMMINE ION (2 entities in total)
• Functional Keywords: rna maturation, exoribonuclease resistance, viral non-coding rna, rna
• Biological source: Sweet clover necrotic mosaic virus
• Total number of polymer chains: 1
• Total formula weight: 17487.73

Authors

Steckelberg, A.-L.,Akiyama, B.M.,Costantino, D.A.,Sit, T.L.,Nix, J.C.,Kieft, J.S. (deposition date: 2018-04-16, release date: 2018-06-20, Last modification date: 2024-03-13)

Primary citation

Steckelberg, A.L.,Akiyama, B.M.,Costantino, D.A.,Sit, T.L.,Nix, J.C.,Kieft, J.S.
A folded viral noncoding RNA blocks host cell exoribonucleases through a conformationally dynamic RNA structure.
Proc. Natl. Acad. Sci. U.S.A., 115:6404-6409, 2018

PubMed 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.

PubMed: 29866852
DOI: 10.1073/pnas.1802429115

Experimental method

X-RAY DIFFRACTION (2.9 Å)