PXD032318-1

PXD032318 is an original dataset announced via ProteomeXchange.

Title	Kaposi’s sarcoma-associated herpesvirus induces specialised ribosomes to efficiently translate viral lytic mRNAs
Description	Historically, 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.
HostingRepository	PRIDE
AnnounceDate	2022-12-21
AnnouncementXML	Submission_2022-12-21_12:03:17.118.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JamesMurphy
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Human herpesvirus 8 strain rKSHV.219; NCBI TaxID: 651668;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-16 04:12:20	ID requested
⏵ 1	2022-12-21 12:03:17	announced

Dataset with its publication pending

submitter keyword: Microbiology/Virology/Herpes virus/Human/Specalised Ribosome/Ribosome Biogenesis

AdrianWhitehouse
contact affiliation	School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, United Kingdom
contact email	a.whitehouse@leeds.ac.uk
lab head
JamesMurphy
contact affiliation	University of Leeds
contact email	bs12jcm@leeds.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD032318
     1. Label: PRIDE project
     2. Name: Kaposi’s sarcoma-associated herpesvirus induces specialised ribosomes to efficiently translate viral lytic mRNAs