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RNA structures that resist degradation by Xrn1 produce a pathogenic Dengue virus RNA.
Elife 2014; 3:e01892E

Abstract

Dengue virus is a growing global health threat. Dengue and other flaviviruses commandeer the host cell's RNA degradation machinery to generate the small flaviviral RNA (sfRNA), a noncoding RNA that induces cytopathicity and pathogenesis. Host cell exonuclease Xrn1 likely loads on the 5' end of viral genomic RNA and degrades processively through ∼10 kB of RNA, halting near the 3' end of the viral RNA. The surviving RNA is the sfRNA. We interrogated the architecture of the complete Dengue 2 sfRNA, identifying five independently-folded RNA structures, two of which quantitatively confer Xrn1 resistance. We developed an assay for real-time monitoring of Xrn1 resistance that we used with mutagenesis and RNA folding experiments to show that Xrn1-resistant RNAs adopt a specific fold organized around a three-way junction. Disrupting the junction's fold eliminates the buildup of disease-related sfRNAs in human cells infected with a flavivirus, directly linking RNA structure to sfRNA production. DOI: http://dx.doi.org/10.7554/eLife.01892.001.

Authors+Show Affiliations

Department of Biochemistry and Molecular Genetics, Howard Hughes Medical Institute, University of Colorado Denver School of Medicine, Aurora, United States.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24692447

Citation

Chapman, Erich G., et al. "RNA Structures That Resist Degradation By Xrn1 Produce a Pathogenic Dengue Virus RNA." ELife, vol. 3, 2014, pp. e01892.
Chapman EG, Moon SL, Wilusz J, et al. RNA structures that resist degradation by Xrn1 produce a pathogenic Dengue virus RNA. Elife. 2014;3:e01892.
Chapman, E. G., Moon, S. L., Wilusz, J., & Kieft, J. S. (2014). RNA structures that resist degradation by Xrn1 produce a pathogenic Dengue virus RNA. ELife, 3, pp. e01892. doi:10.7554/eLife.01892.
Chapman EG, et al. RNA Structures That Resist Degradation By Xrn1 Produce a Pathogenic Dengue Virus RNA. Elife. 2014 Apr 1;3:e01892. PubMed PMID: 24692447.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - RNA structures that resist degradation by Xrn1 produce a pathogenic Dengue virus RNA. AU - Chapman,Erich G, AU - Moon,Stephanie L, AU - Wilusz,Jeffrey, AU - Kieft,Jeffrey S, Y1 - 2014/04/01/ PY - 2014/4/3/entrez PY - 2014/4/3/pubmed PY - 2014/4/3/medline KW - 3′UTR KW - Xrn1 KW - dengue virus KW - exonuclease resistance KW - small flavivirus RNA KW - xrRNA SP - e01892 EP - e01892 JF - eLife JO - Elife VL - 3 N2 - Dengue virus is a growing global health threat. Dengue and other flaviviruses commandeer the host cell's RNA degradation machinery to generate the small flaviviral RNA (sfRNA), a noncoding RNA that induces cytopathicity and pathogenesis. Host cell exonuclease Xrn1 likely loads on the 5' end of viral genomic RNA and degrades processively through ∼10 kB of RNA, halting near the 3' end of the viral RNA. The surviving RNA is the sfRNA. We interrogated the architecture of the complete Dengue 2 sfRNA, identifying five independently-folded RNA structures, two of which quantitatively confer Xrn1 resistance. We developed an assay for real-time monitoring of Xrn1 resistance that we used with mutagenesis and RNA folding experiments to show that Xrn1-resistant RNAs adopt a specific fold organized around a three-way junction. Disrupting the junction's fold eliminates the buildup of disease-related sfRNAs in human cells infected with a flavivirus, directly linking RNA structure to sfRNA production. DOI: http://dx.doi.org/10.7554/eLife.01892.001. SN - 2050-084X UR - https://www.unboundmedicine.com/medline/citation/24692447/RNA_structures_that_resist_degradation_by_Xrn1_produce_a_pathogenic_Dengue_virus_RNA_ L2 - https://doi.org/10.7554/eLife.01892 DB - PRIME DP - Unbound Medicine ER -