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

by Aspden, Julie L. , Trevelyan, Christopher J. , Menezes, Sarah , Macdonald, Andrew , Wilson, Stuart A. , Manners, Oliver , Yonchev, Ivaylo D. , Whitehouse, Adrian , Baquero-Perez, Belinda , Harper, Katherine L. , Mottram, Timothy J. , Patterson, Molly R.

in Adenosine / Antibodies / cell signalling / Gene expression / GPCR5A / Herpes viruses / Infections / Kaposi's sarcoma / KSHV / Lymphoma / lytic replication / m6A methylation / mammals / mRNA stability / Mutagenesis / N6-methyladenosine / NF-κB protein / Plasmids / Proteins / Replication / RNA modification / Sarcoma / Signal transduction / topology / transcriptome / Transcriptomes / Viral infections / Viruses

2023

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

2023

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

2023

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Journal Article

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

Aspden, Julie L.,

Trevelyan, Christopher J.,

Menezes, Sarah,

Macdonald, Andrew,

Wilson, Stuart A.,

Manners, Oliver,

Yonchev, Ivaylo D.,

Whitehouse, Adrian,

Baquero-Perez, Belinda,

Harper, Katherine L.,

Mottram, Timothy J.,

Patterson, Molly R.

2023

Overview

The epitranscriptomic modification N6-methyladenosine (m6A) 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 m6A topology upon both viral and cellular mRNAs within infected cells. Here we investigate the role of m6A in cellular transcripts upregulated during KSHV lytic replication. Our results show that m6A 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 NFκB signalling. Overall, this work highlights the central importance of m6A in modulating cellular gene expression to influence viral infection.

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Publisher

MDPI AG,MDPI

Subject

/ GPCR5A