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Musashi Binding Elements in Zika and Related Flavivirus 3'UTRs
Emerging and re-emerging arthropod-borne viruses such as Japanese encephalitis (JEV), Dengue (DENV), Yellow fever (YFV), and Chikungunya (CHIKV) viruses are a growing global health threat. Zika virus (ZIKV) is a neurotropic flavivirus (FV) that can cause congenital infection, which can result in microcephaly and fetal demise. Recently, the translational regulator protein Musashi-1 (Msi1) has been attributed to promoting ZIKV replication, neurotropism, and pathology. Msi1 predominantly binds single-stranded UAG motifs in the 3'UTR of RNA. Here we systematically analyzed the thermodynamic properties of Musashi binding elements (MBEs) in the 3'UTR of 76 arbovirus genomes in silico. Our results indicate that MBEs in the ZIKV 3'UTR occur predominantly in unpaired, single-stranded structural context, thus supporting experimental observations of Msi1 binding affinity with a thermodynamic model of RNA structure formation.