PT  - JOURNAL ARTICLE
AU  - Adriano de Bernardi Schneider
AU  - Michael T. Wolfinger
TI  - Musashi binding elements in Zika and related Flavivirus 3’UTRs: A comparative study <em>in silico</em>
AID  - 10.1101/407833
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 407833
4099  - http://biorxiv.org/content/early/2018/09/04/407833.short
4100  - http://biorxiv.org/content/early/2018/09/04/407833.full
AB  - 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 3’UTR of RNA. We systematically analyzed the properties of Musashi binding elements (MBEs) in the 3’UTR of flaviviruses based on a thermodynamic model for RNA folding. Our results indicate that MBEs in ZIKV 3’UTRs 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.