Characterizing Expression and Regulation of Gamma-Herpesviral Circular RNAs.
Tagawa, T., D. Oh, J. Santos, S. Dremel, G. Mahesh, T.S. Uldrick, R. Yarchoan, V.N. Kopardé, and J.M. Ziegelbauer. 2021. Characterizing Expression and Regulation of Gamma-Herpesviral Circular RNAs. Front Microbiol. 12:670542. doi:10.3389/fmicb.2021.670542.
Multiple herpesviruses have been recently found to encode viral circular RNAs. Likecellular circular RNAs, these RNAs lack poly-A tails and their 5′ and 3′ ends havebeen joined, which confers protection from RNA exonucleases. We examined theexpression patterns of circular RNAs from Kaposi’s sarcoma herpesvirus (KSHV) invarious environments. We performed deep sequencing of circRNA-enriched total RNAfrom a KSHV-positive patient lymph node for comparison with previous circRNA-Seqresults. We found that circvIRF4 is highly expressed in the KSHV-positive patient samplerelative to both B cell lines and de novo infected primary vascular and lymphaticendothelial cells (LECs). Overall, this patient sample showed a viral circRNA expressionpattern more similar to the pattern from B cell lines, but we also discovered new back-spliced junctions and additional viral circular RNAs in this patient sample. We validatedsome of these back-spliced junctions as circular RNAs with standard assays. Differentialexpression patterns of circular RNAs in different cell types led us to investigate whatcellular factors might be influencing the ratio of viral linear mRNAs to circular RNAs.We found that repression of certain RNA-binding proteins shifted the balance betweenviral linear mRNAs and circular RNAs. Taken together, examining viral circular RNAexpression patterns may become useful tools for discovering their functions, theregulators of their expression, and determining the stage and cell types of infectionin humans.