m 6 A Regulates the Stability of Cellular Transcripts Required for Efficient KSHV Lytic Replication

The epitranscriptomic modification -methyladenosine (m 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 herpesv...

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Bibliographic Details
Published inViruses Vol. 15; no. 6
Main Authors Manners, Oliver, Baquero-Perez, Belinda, Mottram, Timothy J, Yonchev, Ivaylo D, Trevelyan, Christopher J, Harper, Katherine L, Menezes, Sarah, Patterson, Molly R, Macdonald, Andrew, Wilson, Stuart A, Aspden, Julie L, Whitehouse, Adrian
Format Journal Article
LanguageEnglish
Published Switzerland 16.06.2023
Subjects
Cell Line, Tumor
Gene Expression Regulation, Viral
Herpesvirus 8, Human - genetics
RNA, Messenger - genetics
Signal Transduction
Virus Latency - genetics
Virus Replication
m6A methylation
RNA modification
KSHV
cell signalling
lytic replication
GPCR5A
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Summary:The epitranscriptomic modification -methyladenosine (m 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 A topology upon both viral and cellular mRNAs within infected cells. Here we investigate the role of m A in cellular transcripts upregulated during KSHV lytic replication. Our results show that m A is crucial for the stability of the 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 NFκB signalling. Overall, this work highlights the central importance of m A in modulating cellular gene expression to influence viral infection.
ISSN:1999-4915