Circular RNAs and RNase L in PKR activation and virus infection

A proposed model depicting a circRNA shuttling with nuclear acid receptors from the nucleus to the cytoplasm to act as a PKR inhibitor. The illustration based on the report [5] shows a newly formed circRNA with two short dsRNA stems in association with nuclear NF90 (ILF3 isoform-2) [8, 9]. After exported with a circRNA to the cytoplasm, NF90 is released from the cytoplasmic circRNA and replaced by cytoplasmic PKR. The free NF90 will either shuttle back to the nucleus or subjects to protein degradation in the cytoplasm. Thus, the cytoplasmic circRNA serves as a PKR sponge and prevents PKR activation. Activated RNase L by RNA virus infection or by poly I:C stimulation binds to the circRNA single-stranded regions, leading to rapid circRNA decay and release of PKR for PKR activatio