Murphy et al. 2022 (PRJNA818335)

General Details

Title Kaposi’s sarcoma-associated herpesvirus induces specialized ribosomes to efficiently translate viral lytic mRNAs
Organism
Number of Samples 4
Release Date 2022/03/21 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP365126
ENA SRP365126
GEO GSE199095
BioProject PRJNA818335

Publication

Title
Authors Murphy JC,Harrington EM,Schumann S,Vasconcelos EJR,Mottram TJ,Harper KL,Aspden JL,Whitehouse A
Journal Nature communications
Publication Date 2023 Jan 18
Abstract 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).
PMC PMC9849454
PMID 36653366
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR18402610 PRJNA818335 Homo sapiens TREx BCBL1-Rta Ribo-Seq
SRR18402611 PRJNA818335 Homo sapiens TREx BCBL1-Rta Ribo-Seq
SRR18402614 PRJNA818335 Homo sapiens TREx BCBL1-Rta Ribo-Seq
SRR18402615 PRJNA818335 Homo sapiens TREx BCBL1-Rta Ribo-Seq
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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