TY - JOUR TI - 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 A2 - Nilsen, Timothy VL - 3 PY - 2014 DA - 2014/04/01 SP - e01892 C1 - eLife 2014;3:e01892 DO - 10.7554/eLife.01892 UR - https://doi.org/10.7554/eLife.01892 AB - 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. KW - Xrn1 KW - dengue virus KW - exonuclease resistance KW - xrRNA KW - small flavivirus RNA KW - 3′UTR JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -