Dataset Information

M⁶A Regulates the Stability of Cellular Transcripts Required for Efficient KSHV Lytic Replication.

ABSTRACT: 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.

SUBMITTER: Manners O

PROVIDER: S-EPMC10303434 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Manners Oliver O Baquero-Perez Belinda B Mottram Timothy J TJ Yonchev Ivaylo D ID Trevelyan Christopher J CJ Harper Katherine L KL Menezes Sarah S Patterson Molly R MR Macdonald Andrew A Wilson Stuart A SA Aspden Julie L JL Whitehouse Adrian A

Viruses 20230616 6

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 invest ...[more]

PMID: 37376680

Similar Datasets

Project description:Kaposi's sarcoma-associated herpesvirus (KSHV) relies on many cellular proteins to complete replication and generate new virions. Paraspeckle nuclear bodies consisting of core ribonucleoproteins splicing factor proline/glutamine-rich (SFPQ), Non-POU domain-containing octamer-binding protein (NONO), and paraspeckle protein component 1 (PSPC1) along with the long non-coding RNA NEAT1, form a complex that has been speculated to play an important role in viral replication. Paraspeckle bodies are multifunctional and involved in various processes including gene expression, mRNA splicing, and anti-viral defenses. To better understand the role of SFPQ during KSHV replication, we performed SFPQ immunoprecipitation followed by mass spectrometry from KSHV-infected cells. Proteomic analysis showed that during lytic reactivation, SFPQ associates with viral proteins, including ORF10, ORF59, and ORF61. These results are consistent with a previously reported ORF59 proteomics assay identifying SFPQ. To test if the association between ORF59 and SFPQ is important for replication, we first identified the region of ORF59 that associates with SFPQ using a series of 50 amino acid deletion mutants of ORF59 in the KSHV BACmid system. By performing co-immunoprecipitations, we identified the region spanning amino acids 101-150 of ORF59 as the association domain with SFPQ. Using this information, we generated a dominant negative polypeptide of ORF59 encompassing amino acids 101-150, that disrupted the association between SFPQ and full-length ORF59, and decreased virus production. Interestingly, when we tested other human herpesvirus processivity factors (EBV BMRF1, HSV-1 UL42, and HCMV UL44) by transfection of each expression plasmid followed by co-immunoprecipitation, we found a conserved association with SFPQ. These are limited studies that remain to be done in the context of infection but suggest a potential association of SFPQ with processivity factors across multiple herpesviruses.

Dataset Information

M⁶A Regulates the Stability of Cellular Transcripts Required for Efficient KSHV Lytic Replication.

Publications

m<sup>6</sup>A Regulates the Stability of Cellular Transcripts Required for Efficient KSHV Lytic Replication.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

M6A Regulates the Stability of Cellular Transcripts Required for Efficient KSHV Lytic Replication.

Publications

m<sup>6</sup>A Regulates the Stability of Cellular Transcripts Required for Efficient KSHV Lytic Replication.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

M⁶A Regulates the Stability of Cellular Transcripts Required for Efficient KSHV Lytic Replication.