GSE117798
Circular DNA tumor viruses make circular RNAs
Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) cause ~2% of all  human cancers. RNase R-resistant RNA sequencing revealed that both  gammaherpesviruses encode multiple, uniquely stable, circular RNAs (circRNA). EBV  abundantly expressed both exon-only and exon-intron circRNAs from the BART locus  (circBARTs) formed from a spliced BART transcript and excluding the EBV miRNA  region. CircBARTs were expressed in all verified EBV latency types, including EBV-  positive post-transplant lymphoproliferative disease (PTLD), Burkitt lymphoma,  nasopharyngeal carcinoma, and AIDS-associated lymphoma tissues and cell lines. Only  cells infected with the B95-8 EBV strain, with a 12-kb BART locus deletion, were  negative for EBV circBARTs. Less abundant levels of EBV circRNAs originating from  LMP2 and BHLF1-encoding genes were also identified. CircRNA sequencing of KSHV-  infected PEL cells revealed a KSHV-encoded circRNA from the vIRF4 locus (circvIRF4)  that was constitutively expressed. In addition, KSHV polyadenylated nuclear (PAN) RNA  locus generated a swarm (>100) of multiply backspliced, low-abundance RNase R-  resistant circRNAs originating in both sense and antisense directions consistent with a  novel hyper-backsplicing mechanism. In EBV and KSHV co-infected cells, exon-only  EBV circBARTS were located more in the cytoplasm, whereas the intron-retaining  circBARTs were found in the nuclear fraction. KSHV circvIRF4 and circPANs were  detected in both nuclear and cytoplasmic fractions. Among viral circRNAs tested, none  were found in polysome fractions from KSHV-EBV co-infected BC1 cells although low  abundance protein translation from viral circRNAs could not be excluded. CircRNAs are  a new class of viral transcripts expressed in gammaherpesvirus-related tumors that  might contribute to viral oncogenesis. Overall design: Ribodepleted, RnaseR treated RNA from EBV/KSHV positive or negative tissue or cell lines was used for RNA sequencing