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Record number 532011
Title Mechanism and structural diversity of exoribonuclease-resistant RNA structures in flaviviral RNAs
Author(s) Macfadden, Andrea; O’Donoghue, Zoe; Silva, Patricia A.G.C.; Chapman, Erich G.; Olsthoorn, René C.; Sterken, Mark G.; Pijlman, Gorben P.; Bredenbeek, Peter J.; Kieft, Jeffrey S.
Source Nature Communications 9 (2018)1. - ISSN 2041-1723
DOI http://dx.doi.org/10.1038/s41467-017-02604-y
Department(s) Laboratory of Nematology
PE&RC
Laboratory of Virology
Publication type Refereed Article in a scientific journal
Publication year 2018
Abstract Flaviviruses such as Yellow fever, Dengue, West Nile, and Zika generate disease-linked viral noncoding RNAs called subgenomic flavivirus RNAs. Subgenomic flavivirus RNAs result when the 5′–3′ progression of cellular exoribonuclease Xrn1 is blocked by RNA elements called Xrn1-resistant RNAs located within the viral genome’s 3′-untranslated region that operate without protein co-factors. Here, we show that Xrn1-resistant RNAs can halt diverse exoribonucleases, revealing a mechanism in which they act as general mechanical blocks that ‘brace’ against an enzyme’s surface, presenting an unfolding problem that confounds further enzyme progression. Further, we directly demonstrate that Xrn1-resistant RNAs exist in a diverse set of flaviviruses, including some specific to insects or with no known arthropod vector. These Xrn1-resistant RNAs comprise two secondary structural classes that mirror previously reported phylogenic analysis. Our discoveries have implications for the evolution of exoribonuclease resistance, the use of Xrn1-resistant RNAs in synthetic biology, and the development of new therapies.
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