GSE212350
A-to-I editing is a major contributor to viral and cellular transcriptome diversity in primary effusion lymphoma
RNA editing is a major contributor to transcriptome diversity with far reaching biological consequences. Adenosine to Inosine (A-to-I) RNA editing is the most common type of RNA editing in animals and is carried out by a family of proteins called adenosine deaminases acting on RNAs (ADARs). Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of several human malignancies including primary effusion lymphoma (PEL). The extent of RNA editing within the KSHV transcriptome in PEL is unclear as is its contribution to regulating the KSHV lifecycle. Herein, we leverage a combination of biochemical and genomic approaches to determine the RNA editing landscape in host- and KSHV transcriptomes during reactivation in PEL. Analysis of host editomes indicates the editing efficiency is increased in reactivation and by analyzing BCBL1 and BC-3 editomes, we discover conserved as well as cell type specific editing events. In addition, we de novo predict and validate viral editing sites within KSHV pre-miR-K12-4. Editing at the stem region regulates miRNA biogenesis while editing within the seed region of mature miR-K12-3p regulates miRNA target specificity and viral transmission. Together, these results expand the transcriptome of PEL cells and describe a role for A-to-I editing KSHV miRNA biogenesis and target specificity. Overall design: We collected latent and lytic BCBL1 and BC-3 cells 48 h post-dox induction and prepared rRNA-depleted RNA-sequencing libraries generating approximately 100 million reads per biological replicate.