The alternative splicing of pre-mRNAs expands a single genetic blueprint to encode multiple, functionally diverse protein isoforms. Viruses have previously been shown to interact with, depend on, and alter host splicing machinery. The consequences, however, incited by viral infection on the global alternative slicing (AS) landscape are under-appreciated. Here, we investigated the transcriptional and alternative splicing profile of neuronal cells infected with a contemporary Puerto Rican Zika virus (ZIKV^PR) isolate, an isolate of the prototypical Ugandan ZIKV (ZIKV^MR), and dengue virus 2 (DENV2). Our analyses revealed that ZIKV^PR induced significantly more differential changes in expressed genes compared to ZIKV^MR or DENV2, despite all three viruses showing equivalent infectivity and viral RNA levels. Consistent with the transcriptional profile, ZIKV^PR induced a higher number of alternative splicing events compared to ZIKV^MR or DENV2, and gene ontology analyses highlighted alternative splicing changes in genes associated with mRNA splicing. In summary, we show that ZIKV affects cellular RNA homeostasis not only at the transcriptional levels but also through the alternative splicing of cellular transcripts. These findings could provide new molecular insights into the neuropathologies associated with this virus.

Eukaroytic RNA‐binding proteins (RBPs) recognize and process RNAs through recognition of their sequence motifs via RNA‐binding domains (RBDs). RBPs usually consist of one or more RBDs and can include additional functional domains that modify or cleave RNA. Engineered RBPs have been used to answer basic biology questions, control gene expression, locate viral RNA in vivo, as well as many other tasks. Given the growing number of diseases associated with RNA and RBPs, engineered RBPs also have the potential to serve as therapeutics. This review provides an in depth description of recent advances in engineered RBPs and discusses opportunities and challenges in the field.This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition RNA Methods > RNA Nanotechnology RNA in Disease and Development > RNA in Disease

The cover image is based on the Review Article The Potential of Engineered Eukaryotic RNA‐Binding Proteins as Molecular Tools and Therapeutics, by Carl R. Shotwell, John Cleary, Andy Berglund. https://doi.org/10.1002/wrna.1573 image