Methylation of KSHV vCyclin by PRMT5 contributes to cell cycle progression and cell proliferation

• DOI: 10.1371/journal.ppat.1012535
• Publication Date: 2024-09-10T17:30:49Z
• Authors: Danping Niu; Yuanming Ma; Pengyu Ren; Sijia Chang; Chenhui Li; Yong Jiang; Chunyan Han; Ke Lan
• Keywords: Kaposi's sarcoma-associated herpesvirus; Retinoblastoma protein

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus that encodes numerous cellular homologs, including cyclin D, G protein-coupled protein, interleukin-6, and macrophage inflammatory proteins 1 2. KSHV vCyclin encoded by ORF72, the homolog of cyclinD2. can regulate replication cell proliferation constitutively activating cyclin-dependent kinase 6 (CDK6). However, regulatory mechanism has not been fully elucidated. In present study, we identified host protein named arginine methyltransferase 5 (PRMT5) interacts with vCyclin. We further demonstrated PRMT5 upregulated latency-associated nuclear antigen (LANA) through transcriptional activation. Remarkably, knockdown or pharmaceutical inhibition (using EPZ015666) inhibited cycle progression latently infected tumor cells. Mechanistically, methylates symmetrically at 128 stabilizes in activity-dependent manner. also show methylation positively regulates phosphorylate retinoblastoma (pRB) pathway. Taken together, our findings reveal an important effect on facilitates proliferation, which provides potential therapeutic target for KSHV-associated malignancies.