Tags

Type your tag names separated by a space and hit enter

New hypotheses derived from the structure of a flaviviral Xrn1-resistant RNA: Conservation, folding, and host adaptation.
RNA Biol 2015; 12(11):1169-77RB

Abstract

Arthropod-borne flaviviruses (FVs) are a growing world-wide health threat whose incidence and range are increasing. The pathogenicity and cytopathicity of these single-stranded RNA viruses are influenced by viral subgenomic non-protein-coding RNAs (sfRNAs) that the viruses produce to high levels during infection. To generate sfRNAs the virus co-opts the action of the abundant cellular exonuclease Xrn1, which is part of the cell's normal RNA turnover machinery. This exploitation of the cellular machinery is enabled by discrete, highly structured, Xrn1-resistant RNA elements (xrRNAs) in the 3'UTR that interact with Xrn1 to halt processive 5' to 3' decay of the viral genomic RNA. We recently solved the crystal structure of a functional xrRNA, revealing a novel fold that provides a mechanistic model for Xrn1 resistance. Continued analysis and interpretation of the structure reveals that the tertiary contacts that knit the xrRNA fold together are shared by a wide variety of arthropod-borne FVs, conferring robust Xrn1 resistance in all tested. However, there is some variability in the structures that correlates with unexplained patterns in the viral 3' UTRs. Finally, examination of these structures and their behavior in the context of viral infection leads to a new hypothesis linking RNA tertiary structure, overall 3' UTR architecture, sfRNA production, and host adaptation.

Authors+Show Affiliations

a Department of Biochemistry and Molecular Genetics. b Howard Hughes Medical Institute; University of Colorado Denver; School of Medicine ; Aurora , CO USA.c Department of Pediatrics ; University of Colorado Denver; School of Medicine ; Aurora , CO USA.a Department of Biochemistry and Molecular Genetics.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

26399159

Citation

Kieft, Jeffrey S., et al. "New Hypotheses Derived From the Structure of a Flaviviral Xrn1-resistant RNA: Conservation, Folding, and Host Adaptation." RNA Biology, vol. 12, no. 11, 2015, pp. 1169-77.
Kieft JS, Rabe JL, Chapman EG. New hypotheses derived from the structure of a flaviviral Xrn1-resistant RNA: Conservation, folding, and host adaptation. RNA Biol. 2015;12(11):1169-77.
Kieft, J. S., Rabe, J. L., & Chapman, E. G. (2015). New hypotheses derived from the structure of a flaviviral Xrn1-resistant RNA: Conservation, folding, and host adaptation. RNA Biology, 12(11), pp. 1169-77. doi:10.1080/15476286.2015.1094599.
Kieft JS, Rabe JL, Chapman EG. New Hypotheses Derived From the Structure of a Flaviviral Xrn1-resistant RNA: Conservation, Folding, and Host Adaptation. RNA Biol. 2015;12(11):1169-77. PubMed PMID: 26399159.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - New hypotheses derived from the structure of a flaviviral Xrn1-resistant RNA: Conservation, folding, and host adaptation. AU - Kieft,Jeffrey S, AU - Rabe,Jennifer L, AU - Chapman,Erich G, Y1 - 2015/09/23/ PY - 2015/9/25/entrez PY - 2015/9/25/pubmed PY - 2016/9/16/medline KW - RNA folding KW - RNA structure KW - Xrn1 resistance KW - flaviviral RNA KW - sfRNA SP - 1169 EP - 77 JF - RNA biology JO - RNA Biol VL - 12 IS - 11 N2 - Arthropod-borne flaviviruses (FVs) are a growing world-wide health threat whose incidence and range are increasing. The pathogenicity and cytopathicity of these single-stranded RNA viruses are influenced by viral subgenomic non-protein-coding RNAs (sfRNAs) that the viruses produce to high levels during infection. To generate sfRNAs the virus co-opts the action of the abundant cellular exonuclease Xrn1, which is part of the cell's normal RNA turnover machinery. This exploitation of the cellular machinery is enabled by discrete, highly structured, Xrn1-resistant RNA elements (xrRNAs) in the 3'UTR that interact with Xrn1 to halt processive 5' to 3' decay of the viral genomic RNA. We recently solved the crystal structure of a functional xrRNA, revealing a novel fold that provides a mechanistic model for Xrn1 resistance. Continued analysis and interpretation of the structure reveals that the tertiary contacts that knit the xrRNA fold together are shared by a wide variety of arthropod-borne FVs, conferring robust Xrn1 resistance in all tested. However, there is some variability in the structures that correlates with unexplained patterns in the viral 3' UTRs. Finally, examination of these structures and their behavior in the context of viral infection leads to a new hypothesis linking RNA tertiary structure, overall 3' UTR architecture, sfRNA production, and host adaptation. SN - 1555-8584 UR - https://www.unboundmedicine.com/medline/citation/26399159/New_hypotheses_derived_from_the_structure_of_a_flaviviral_Xrn1_resistant_RNA:_Conservation_folding_and_host_adaptation_ L2 - http://www.tandfonline.com/doi/full/10.1080/15476286.2015.1094599 DB - PRIME DP - Unbound Medicine ER -