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An RNA pseudoknot is required for production of yellow fever virus subgenomic RNA by the host nuclease XRN1.
J Virol 2010; 84(21):11395-406JV

Abstract

Cells and mice infected with arthropod-borne flaviviruses produce a small subgenomic RNA that is colinear with the distal part of the viral 3'-untranslated region (UTR). This small subgenomic flavivirus RNA (sfRNA) results from the incomplete degradation of the viral genome by the host 5'-3' exonuclease XRN1. Production of the sfRNA is important for the pathogenicity of the virus. This study not only presents a detailed description of the yellow fever virus (YFV) sfRNA but, more importantly, describes for the first time the molecular characteristics of the stalling site for XRN1 in the flavivirus genome. Similar to the case for West Nile virus, the YFV sfRNA was produced by XRN1. However, in contrast to the case for other arthropod-borne flaviviruses, not one but two sfRNAs were detected in YFV-infected mammalian cells. The smaller of these two sfRNAs was not observed in infected mosquito cells. The larger sfRNA could also be produced in vitro by incubation with purified XRN1. These two YFV sfRNAs formed a 5'-nested set. The 5' ends of the YFV sfRNAs were found to be just upstream of the previously predicted RNA pseudoknot PSK3. RNA structure probing and mutagenesis studies provided strong evidence that this pseudoknot structure was formed and served as the molecular signal to stall XRN1. The sequence involved in PSK3 formation was cloned into the Sinrep5 expression vector and shown to direct the production of an sfRNA-like RNA. These results underscore the importance of the RNA pseudoknot in stalling XRN1 and also demonstrate that it is the sole viral requirement for sfRNA production.

Authors+Show Affiliations

Department of Medical Microbiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20739539

Citation

Silva, Patrícia A G C., et al. "An RNA Pseudoknot Is Required for Production of Yellow Fever Virus Subgenomic RNA By the Host Nuclease XRN1." Journal of Virology, vol. 84, no. 21, 2010, pp. 11395-406.
Silva PA, Pereira CF, Dalebout TJ, et al. An RNA pseudoknot is required for production of yellow fever virus subgenomic RNA by the host nuclease XRN1. J Virol. 2010;84(21):11395-406.
Silva, P. A., Pereira, C. F., Dalebout, T. J., Spaan, W. J., & Bredenbeek, P. J. (2010). An RNA pseudoknot is required for production of yellow fever virus subgenomic RNA by the host nuclease XRN1. Journal of Virology, 84(21), pp. 11395-406. doi:10.1128/JVI.01047-10.
Silva PA, et al. An RNA Pseudoknot Is Required for Production of Yellow Fever Virus Subgenomic RNA By the Host Nuclease XRN1. J Virol. 2010;84(21):11395-406. PubMed PMID: 20739539.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An RNA pseudoknot is required for production of yellow fever virus subgenomic RNA by the host nuclease XRN1. AU - Silva,Patrícia A G C, AU - Pereira,Carina F, AU - Dalebout,Tim J, AU - Spaan,Willy J M, AU - Bredenbeek,Peter J, Y1 - 2010/08/25/ PY - 2010/8/27/entrez PY - 2010/8/27/pubmed PY - 2010/11/5/medline SP - 11395 EP - 406 JF - Journal of virology JO - J. Virol. VL - 84 IS - 21 N2 - Cells and mice infected with arthropod-borne flaviviruses produce a small subgenomic RNA that is colinear with the distal part of the viral 3'-untranslated region (UTR). This small subgenomic flavivirus RNA (sfRNA) results from the incomplete degradation of the viral genome by the host 5'-3' exonuclease XRN1. Production of the sfRNA is important for the pathogenicity of the virus. This study not only presents a detailed description of the yellow fever virus (YFV) sfRNA but, more importantly, describes for the first time the molecular characteristics of the stalling site for XRN1 in the flavivirus genome. Similar to the case for West Nile virus, the YFV sfRNA was produced by XRN1. However, in contrast to the case for other arthropod-borne flaviviruses, not one but two sfRNAs were detected in YFV-infected mammalian cells. The smaller of these two sfRNAs was not observed in infected mosquito cells. The larger sfRNA could also be produced in vitro by incubation with purified XRN1. These two YFV sfRNAs formed a 5'-nested set. The 5' ends of the YFV sfRNAs were found to be just upstream of the previously predicted RNA pseudoknot PSK3. RNA structure probing and mutagenesis studies provided strong evidence that this pseudoknot structure was formed and served as the molecular signal to stall XRN1. The sequence involved in PSK3 formation was cloned into the Sinrep5 expression vector and shown to direct the production of an sfRNA-like RNA. These results underscore the importance of the RNA pseudoknot in stalling XRN1 and also demonstrate that it is the sole viral requirement for sfRNA production. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/20739539/An_RNA_pseudoknot_is_required_for_production_of_yellow_fever_virus_subgenomic_RNA_by_the_host_nuclease_XRN1_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=20739539 DB - PRIME DP - Unbound Medicine ER -