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

Autor: Manners O; School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK., Baquero-Perez B; Molecular Virology Unit, Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain., Mottram TJ; School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK., Yonchev ID; Sheffield Institute for Nucleic Acids, School of Biosciences, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK., Trevelyan CJ; School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK., Harper KL; School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK., Menezes S; School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK., Patterson MR; School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK., Macdonald A; School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK., Wilson SA; Sheffield Institute for Nucleic Acids, School of Biosciences, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK., Aspden JL; School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.; LeedsOmics, University of Leeds, Leeds LS2 9JT, UK., Whitehouse A; School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.; Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South Africa.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2023 Jun 16; Vol. 15 (6). Date of Electronic Publication: 2023 Jun 16.
DOI: 10.3390/v15061381
Abstrakt: 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 NFκB signalling. Overall, this work highlights the central importance of m 6 A in modulating cellular gene expression to influence viral infection.
Databáze: MEDLINE
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