Figure 6.

Relationship between RIOK3 splicing products, RVFV MP-12 infection, and innate immune activation. The human RIOK3 gene is represented at the top of the panel with its 13 exons. The normal RIOK3 protein with a complete kinase domain is called full-length and produced by translation of a canonically spliced transcript encompassing the 13 exons (left side of figure). Alternative 5′ splice donor usage shortens exon 8 and results in the X2 variant mRNA. Translation of the X2 mRNA would produce a truncated RIOK3 missing most of the kinase domain (right side of figure). Notably, the X2 RNA contains an exonic premature termination codon making it a canonical substrate for nonsense-mediated decay and rapid degradation. The effects on RIOK3 gene expression during MP-12 infection (blue arrows) compared to uninfected cells (orange arrows) are shown. The magnitude of the effect is represented by the thickness of each arrow. It is not known if the X2 variant RIOK3 protein is expressed or stable, or if it possesses any function. By contrast, the full-length RIOK3 protein has been suggested to be involved in several diverse cell functions and pathways (see text), thus the relative expression levels of full length and X2 variants of RIOK3 can have strong effects on cellular functions including the antiviral response.