m6A Regulates the Stability of Cellular Transcripts Required for Efficient KSHV Lytic Replication

The epitranscriptomic modification N-6-methyladenosine (m(6)A) is a ubiquitous feature of the mammalian transcriptome. It modulates mRNA fate and dynamics to exert regulatory control over numerous cellular processes and disease pathways, including viral infection. Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation from the latent phase leads to the redistribution of m(6)A topology upon both viral and cellular mRNAs within infected cells. Here we investigate the role of m(6)A in cellular transcripts upregulated during KSHV lytic replication. Our results show that m(6)A is crucial for the stability of the GPRC5A mRNA, whose expression is induced by the KSHV latent-lytic switch master regulator, the replication and transcription activator (RTA) protein. Moreover, we demonstrate that GPRC5A is essential for efficient KSHV lytic replication by directly regulating NF & kappa;B signalling. Overall, this work highlights the central importance of m(6)A in modulating cellular gene expression to influence viral infection.

Automated summary

The epitranscriptomic modification m(6)A is a ubiquitous feature in mammals, regulating mRNA fate and dynamics and playing a role in viral infection. In this study, the researchers investigated the role of m(6)A in cellular transcripts during KSHV lytic replication. Their results showed that m(6)A is crucial for the stability of GPRC5A mRNA, which is induced by the KSHV latent-lytic switch master regulator RTA protein. Additionally, they demonstrated that GPRC5A is essential for efficient KSHV lytic replication by regulating NF & kappa;B signalling.