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Subgenomic flaviviral RNAs: What do we know after the first decade of research.
Antiviral Res 2018; 159:13-25AR

Abstract

The common feature of flaviviral infection is the accumulation of abundant virus-derived noncoding RNA, named flaviviral subgenomic RNA (sfRNA) in infected cells. This RNA represents a product of incomplete degradation of viral genomic RNA by the cellular 5'-3' exoribonuclease XRN1 that stalls at the conserved highly structured elements in the 3' untranslated region (UTR). This mechanism of sfRNA generation was discovered a decade ago and since then sfRNA has been a focus of intense research. The ability of flaviviruses to produce sfRNA was shown to be evolutionary conserved in all members of Flavivirus genus. Mutations in the 3'UTR that affect production of sfRNAs and their interactions with host factors showed that sfRNAs are responsible for viral pathogenicity, host adaptation, and emergence of new pathogenic strains. RNA structural elements required for XRN1 stalling have been elucidated and the role of sfRNAs in inhibiting host antiviral responses in arthropod and vertebrate hosts has been demonstrated. Some molecular mechanisms determining these properties of sfRNA have been recently characterized, while other aspects of sfRNA functions remain an open avenue for future research. In this review we summarise the current state of knowledge on the mechanisms of generation and functional roles of sfRNAs in the life cycle of flaviviruses and highlight the gaps in our knowledge to be addressed in the future.

Authors+Show Affiliations

The Australian Infectious Disease Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, 4072, Australia.The Australian Infectious Disease Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, 4072, Australia. Electronic address: a.khromykh@uq.edu.au.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

30217649

Citation

Slonchak, Andrii, and Alexander A. Khromykh. "Subgenomic Flaviviral RNAs: what Do We Know After the First Decade of Research." Antiviral Research, vol. 159, 2018, pp. 13-25.
Slonchak A, Khromykh AA. Subgenomic flaviviral RNAs: What do we know after the first decade of research. Antiviral Res. 2018;159:13-25.
Slonchak, A., & Khromykh, A. A. (2018). Subgenomic flaviviral RNAs: What do we know after the first decade of research. Antiviral Research, 159, pp. 13-25. doi:10.1016/j.antiviral.2018.09.006.
Slonchak A, Khromykh AA. Subgenomic Flaviviral RNAs: what Do We Know After the First Decade of Research. Antiviral Res. 2018;159:13-25. PubMed PMID: 30217649.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subgenomic flaviviral RNAs: What do we know after the first decade of research. AU - Slonchak,Andrii, AU - Khromykh,Alexander A, Y1 - 2018/09/11/ PY - 2018/08/02/received PY - 2018/09/10/revised PY - 2018/09/10/accepted PY - 2018/9/16/pubmed PY - 2019/9/24/medline PY - 2018/9/16/entrez KW - Flavivirus KW - Noncoding RNA KW - Subgenomic flaviviral RNA KW - XRN-1 resistance KW - sfRNA SP - 13 EP - 25 JF - Antiviral research JO - Antiviral Res. VL - 159 N2 - The common feature of flaviviral infection is the accumulation of abundant virus-derived noncoding RNA, named flaviviral subgenomic RNA (sfRNA) in infected cells. This RNA represents a product of incomplete degradation of viral genomic RNA by the cellular 5'-3' exoribonuclease XRN1 that stalls at the conserved highly structured elements in the 3' untranslated region (UTR). This mechanism of sfRNA generation was discovered a decade ago and since then sfRNA has been a focus of intense research. The ability of flaviviruses to produce sfRNA was shown to be evolutionary conserved in all members of Flavivirus genus. Mutations in the 3'UTR that affect production of sfRNAs and their interactions with host factors showed that sfRNAs are responsible for viral pathogenicity, host adaptation, and emergence of new pathogenic strains. RNA structural elements required for XRN1 stalling have been elucidated and the role of sfRNAs in inhibiting host antiviral responses in arthropod and vertebrate hosts has been demonstrated. Some molecular mechanisms determining these properties of sfRNA have been recently characterized, while other aspects of sfRNA functions remain an open avenue for future research. In this review we summarise the current state of knowledge on the mechanisms of generation and functional roles of sfRNAs in the life cycle of flaviviruses and highlight the gaps in our knowledge to be addressed in the future. SN - 1872-9096 UR - https://www.unboundmedicine.com/medline/citation/30217649/Subgenomic_flaviviral_RNAs:_What_do_we_know_after_the_first_decade_of_research_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-3542(18)30465-0 DB - PRIME DP - Unbound Medicine ER -