Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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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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