TY - JOUR
T1 - All genera of Flaviviridae host a conserved Xrn1-resistant RNA motif
AU - Dilweg, Ivar W.
AU - Savina, Anya
AU - Köthe, Susanne
AU - Gultyaev, Alexander P.
AU - Bredenbeek, Peter J.
AU - Olsthoorn, René C.L.
N1 - Funding Information:
We acknowledge Jeffrey Kieft for acknowledging R.C.O. and P.J.B. in his previous manuscript on novel xrRNA motifs in the Flaviviridae.
Publisher Copyright:
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021/4/21
Y1 - 2021/4/21
N2 - After infection by flaviviruses like Zika and West Nile virus, eukaryotic hosts employ the well-conserved endoribonuclease Xrn1 to degrade the viral genomic RNA. Within the 3ʹ untranslated regions, this enzyme encounters intricate Xrn1-resistant structures. This results in the accumulation of subgenomic flaviviral RNAs, an event that improves viral growth and aggravates viral pathogenicity. Xrn1-resistant RNAs have been established throughout the flaviviral genus, but not yet throughout the entire Flaviviridae family. In this work, we use previously determined characteristics of these structures to identify homologous sequences in many members of the genera pegivirus, hepacivirus and pestivirus. We used structural alignment and mutational analyses to establish that these sequences indeed represent Xrn1-resistant RNA and that they employ the general features of the flaviviral xrRNAs, consisting of a double pseudoknot formed by five base-paired regions stitched together by a crucial triple base interaction. Furthermore, we demonstrate that the pestivirus Bungowannah virus produces subgenomic RNA in vivo. Altogether, these results indicate that viruses make use of a universal Xrn1-resistant RNA throughout the Flaviviridae family.
AB - After infection by flaviviruses like Zika and West Nile virus, eukaryotic hosts employ the well-conserved endoribonuclease Xrn1 to degrade the viral genomic RNA. Within the 3ʹ untranslated regions, this enzyme encounters intricate Xrn1-resistant structures. This results in the accumulation of subgenomic flaviviral RNAs, an event that improves viral growth and aggravates viral pathogenicity. Xrn1-resistant RNAs have been established throughout the flaviviral genus, but not yet throughout the entire Flaviviridae family. In this work, we use previously determined characteristics of these structures to identify homologous sequences in many members of the genera pegivirus, hepacivirus and pestivirus. We used structural alignment and mutational analyses to establish that these sequences indeed represent Xrn1-resistant RNA and that they employ the general features of the flaviviral xrRNAs, consisting of a double pseudoknot formed by five base-paired regions stitched together by a crucial triple base interaction. Furthermore, we demonstrate that the pestivirus Bungowannah virus produces subgenomic RNA in vivo. Altogether, these results indicate that viruses make use of a universal Xrn1-resistant RNA throughout the Flaviviridae family.
UR - http://www.scopus.com/inward/record.url?scp=85104811607&partnerID=8YFLogxK
U2 - 10.1080/15476286.2021.1907044
DO - 10.1080/15476286.2021.1907044
M3 - Article
C2 - 33858294
AN - SCOPUS:85104811607
VL - 18
SP - 2321
EP - 2329
JO - RNA Biology
JF - RNA Biology
SN - 1547-6286
IS - 12
ER -