| Popis: |
SUMMARYHerpesviruses express over 100 transcripts, including messenger RNAs, long noncoding RNAs, and microRNAs. Herein, we add to this list by performing circular RNA (circRNA) profiling for Herpes Simplex Virus-1, Kaposi sarcoma-associated herpesvirus (KSHV), and murine gammaherpesvirus 68. Using cell culture and animal models of lytic and latent infection, we identified thousands of back-splicing variants. This included circRNAs derived from viral latency genes (circK12, circLAT). During lytic infection circRNAs tiled the viral genome, with a transcriptional density 4,500-fold greater than the host. We characterized cis- and trans-elements controlling back-splicing and found that lytic infection promoted rampant, sequence-independent back-splicing. Using eCLIP and 4SU-Sequencing, we determined that the KSHV RNA binding protein (ORF57) preferentially bound viral circRNAs and globally promoted accumulation post-transcriptionally. Our work elucidates a unique splicing mechanism driven by late lytic replication and identifies a class of transcripts with potential to function in replication, persistence, or tumorigenesis. |
