RNA structures required for production of subgenomic flavivirus RNA

Funk, Anneke, Truong, Katherine, Nagasaki, Tomoko, Torres, Shessy, Floden, Nadia, Balmori Melian, Ezequiel, Edmonds, Judy, Dong, Hongping, Shi, Pei-Yong and Khromykh, Alexander A. (2010) RNA structures required for production of subgenomic flavivirus RNA. Journal of Virology, 84 21: 11407-11417. doi:10.1128/JVI.01159-10


Author Funk, Anneke
Truong, Katherine
Nagasaki, Tomoko
Torres, Shessy
Floden, Nadia
Balmori Melian, Ezequiel
Edmonds, Judy
Dong, Hongping
Shi, Pei-Yong
Khromykh, Alexander A.
Title RNA structures required for production of subgenomic flavivirus RNA
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
1098-5514
1070-6321
Publication date 2010-11-01
Sub-type Article (original research)
DOI 10.1128/JVI.01159-10
Open Access Status DOI
Volume 84
Issue 21
Start page 11407
End page 11417
Total pages 11
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2011
Language eng
Subject C1
03 Chemical Sciences
110309 Infectious Diseases
1103 Clinical Sciences
Abstract Flaviviruses are a group of single-stranded, positive-sense RNA viruses causing ~100 million infections per year. We have recently shown that flaviviruses produce a unique, small, noncoding RNA (~0.5 kb) derived from the 3' untranslated region (UTR) of the genomic RNA (gRNA), which is required for flavivirus-induced cytopathicity and pathogenicity (G. P. Pijlman et al., Cell Host Microbe, 4: 579-591, 2008). This RNA (subgenomic flavivirus RNA [sfRNA]) is a product of incomplete degradation of gRNA presumably by the cellular 5'-3' exoribonuclease XRN1, which stalls on the rigid secondary structure stem-loop II (SL-II) located at the beginning of the 3' UTR. Mutations or deletions of various secondary structures in the 3' UTR resulted in the loss of full-length sfRNA (sfRNA1) and production of smaller and less abundant sfRNAs (sfRNA2 and sfRNA3). Here, we investigated in detail the importance of West Nile virus Kunjin (WNVKUN) 3' UTR secondary structures as well as tertiary interactions for sfRNA formation. We show that secondary structures SL-IV and dumbbell 1 (DB1) downstream of SL-II are able to prevent further degradation of gRNA when the SL-II structure is deleted, leading to production of sfRNA2 and sfRNA3, respectively. We also show that a number of pseudoknot (PK) interactions, in particular PK1 stabilizing SL-II and PK3 stabilizing DB1, are required for protection of gRNA from nuclease degradation and production of sfRNA. Our results show that PK interactions play a vital role in the production of nuclease-resistant sfRNA, which is essential for viral cytopathicity in cells and pathogenicity in mice. Copyright © 2011 by the American Society for Microbiology.
Keyword West Nile virus
3 untranslated region
Kunjin virus
Secondary structure
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Sun, 24 Oct 2010, 00:07:57 EST