Pervasiveness of exoribonuclease-resistant RNAs in plant viruses suggests new roles for these conserved RNA structures

Abstract

1Exoribonuclease-resistant RNAs (xrRNAs) are discrete folded RNA elements that block the processive 2 degradation of RNA by exoribonucleases. xrRNAs found in the 3¢ untranslated regions (UTRs) of animal-3 infecting flaviviruses and in all three members of the plant-infecting Dianthovirus adopt a complex ring-4 like fold that blocks the exoribonuclease; this ability gives rise to viral non-coding subgenomic RNAs. 5The degree to which these folded RNA elements exist in other viruses and in diverse contexts has been 6 unclear. Using computational tools and biochemical assays, we discovered that xrRNA elements are 7 widely found in viruses belonging to the Tombusviridae and Luteoviridae families of plant-infecting RNA 8 viruses, demonstrating their importance and widespread utility. Unexpectedly, many xrRNAs are located 9 in intergenic regions rather than in the 3´UTR and some are associated with the 5¢ ends of subgenomic 10RNAs with protein-coding potential, suggesting that xrRNAs with similar scaffolds are involved in the 11 maturation or maintenance of diverse subgenomic RNAs, not just the ones generated from the 3¢UTR. 12

A 212-nt long RNA structure in the Tobacco necrosis virus-D RNA genome is resistant to Xrn degradation

“…Other genera in this family may also generate svRNAs, however they may have either been overlooked or dismissed as nonrelevant degradation products (22). Recently, a bioinformatics approach was used to identify additional functional RCNMV-like stalling structures in umbraviruses (family Tombusviridae), as well as polero- and enamoviruses (family Luteoviridae) (53). Moreover, some of the svRNAs identified were predicted to encode proteins, suggesting that they could function as mRNAs for viral protein production.…”

Functional RNA Structures in the 3’UTR of Tick-Borne, Insect-Specific and No-Known-Vector Flaviviruses

“…Moreover, recent studies have identified xrRNA functionality in several phylogenetically distant RNA viruses, such as animal-infecting, segmented viruses of the Bunyaviridae and Arenavividae [63] families, as well as plant-infecting viruses of the Tombusuviridae and Luteoviridae families [64,65]. The interesting question whether exoribonucleases other than Xrn1 would be blocked as well has recently been answered.…”