Kaposi's sarcoma-associated herpesvirus induces specialised ribosomes to efficiently translate viral lytic mRNAs.

Autor: Murphy JC; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK., Harrington EM; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK., Schumann S; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK., Vasconcelos EJR; LeedsOmics, University of Leeds, Leeds, LS2 9JT, UK., Mottram TJ; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK., Harper KL; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK., Aspden JL; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for 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, University of Leeds, Leeds, LS2 9JT, UK. a.whitehouse@leeds.ac.uk.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK. a.whitehouse@leeds.ac.uk.; LeedsOmics, University of Leeds, Leeds, LS2 9JT, UK. a.whitehouse@leeds.ac.uk.; Department of Biochemistry & Microbiology, Rhodes University, Grahamstown, 6140, South Africa. a.whitehouse@leeds.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jan 18; Vol. 14 (1), pp. 300. Date of Electronic Publication: 2023 Jan 18.
DOI: 10.1038/s41467-023-35914-5
Abstrakt: Historically, ribosomes were viewed as unchanged homogeneous macromolecular machines with no regulatory capacity for mRNA translation. An emerging concept is that heterogeneity of ribosomal composition exists, exerting a regulatory function or specificity in translational control. This is supported by recent discoveries identifying compositionally distinct specialised ribosomes that actively regulate mRNA translation. Viruses lack their own translational machinery and impose high translational demands on the host during replication. We explore the possibility that KSHV manipulates ribosome biogenesis producing specialised ribosomes which preferentially translate viral transcripts. Quantitative proteomic analysis identified changes in the stoichiometry and composition of precursor ribosomal complexes during the switch from latent to lytic replication. We demonstrate the enhanced association of ribosomal biogenesis factors BUD23 and NOC4L, and the KSHV ORF11 protein, with small ribosomal subunit precursor complexes during lytic replication. BUD23 depletion resulted in significantly reduced viral gene expression, culminating in dramatic reduction of infectious virion production. Ribosome profiling demonstrated BUD23 is essential for reduced association of ribosomes with KSHV uORFs in late lytic genes, required for the efficient translation of the downstream coding sequence. Results provide mechanistic insights into KSHV-mediated manipulation of cellular ribosome composition inducing a population of specialised ribosomes facilitating efficient translation of viral mRNAs.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: