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bioRxiv · 10.1101/407833

Musashi binding elements in Zika and related Flavivirus 3’UTRs: A comparative study in silico

de Bernardi Schneider, A.·Wolfinger, M. T.
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Abstract

Zika virus (ZIKV) belongs to a class of neurotropic viruses that have the ability to cause congenital infection, which can result in microcephaly or fetal demise. Recently, the RNA-binding protein Musashi-1 (Msi1), which mediates the maintenance and self-renewal of stem cells and acts as a translational regulator, has been associated with promoting ZIKV replication, neurotropism, and pathology. Msi1 predominantly binds to single-stranded UAG motifs in the 3UTR of RNA. We systematically analyzed the properties of Musashi binding elements (MBEs) in the 3UTR of flaviviruses based on a thermodynamic model for RNA folding. Our results indicate that MBEs in ZIKV 3UTRs occur predominantly in unpaired, single-stranded structural context, thus corroborating experimental observations by a biophysical model of RNA structure formation. Statistical analysis and comparison with related viruses shows that ZIKV MBEs are maximally accessible among all mosquito-borne flaviviruses. Our study addresses the broader question whether other emerging arboviruses can cause similar neurotropic effects through the same mechanism in the developing fetus. In this line, we establish a link between the biophysical properties of viral RNA and teratogenicity. Moreover, our thermodynamic model can explain recent experimental findings and predict the Msi1-related neurotropic potential of other viruses.

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de Bernardi Schneider, A., Wolfinger, M. T.. 2018-09-04. Musashi binding elements in Zika and related Flavivirus 3’UTRs: A comparative study in silico. https://doi.org/10.1101/407833

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