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PXD032318-1

PXD032318 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleKaposi’s sarcoma-associated herpesvirus induces specialised ribosomes to efficiently translate viral lytic mRNAs
DescriptionHistorically, ribosomes have been viewed as unchanged homogeneous macromolecular machines with no intrinsic regulatory capacity for mRNA translation. However, an emerging concept is that heterogeneity of ribosomal composition exists, which can exert 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 a high translational demand on the host cell during replication. Here we explore the possibility that Kaposi’s sarcoma-associated herpesvirus (KSHV) can manipulate host ribosome biogenesis during infection to produce specialised ribosomes which preferentially translate viral transcripts. Quantitative proteomic analysis has identified changes in the stoichiometry and composition of precursor ribosomal complexes during the switch from latent to lytic KSHV replication. Intriguingly, we demonstrate the enhanced association of ribosomal biogenesis factors BUD23 and NOC4L, and a previously uncharacterised KSHV lytic protein, ORF11, with small ribosomal subunit precursor complexes during lytic KSHV infection. Notably, BUD23 depletion resulted in significantly reduced viral gene expression and progression through the lytic cascade, culminating in a dramatic reduction of infectious virion production. Importantly, ribosome profiling demonstrated that BUD23 is essential for the reduced association of ribosomes with KSHV uORFs in late lytic genes, required for the efficient translation of the main open reading frame. Together our results provide new mechanistic insights into KSHV-mediated manipulation of cellular ribosome composition inducing a population of specialised ribosomes to facilitate efficient translation of viral mRNAs.
HostingRepositoryPRIDE
AnnounceDate2022-12-21
AnnouncementXMLSubmission_2022-12-21_12:03:17.118.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJamesMurphy
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Human herpesvirus 8 strain rKSHV.219; NCBI TaxID: 651668;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-03-16 04:12:20ID requested
12022-12-21 12:03:17announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Microbiology/Virology/Herpes virus/Human/Specalised Ribosome/Ribosome Biogenesis
Contact List
AdrianWhitehouse
contact affiliationSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, United Kingdom
contact emaila.whitehouse@leeds.ac.uk
lab head
JamesMurphy
contact affiliationUniversity of Leeds
contact emailbs12jcm@leeds.ac.uk
dataset submitter
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Dataset FTP location
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