PXD043115-1

PXD043115 is an original dataset announced via ProteomeXchange.

Title	RpS19a depletion alters the haematopoietic translatome to directly drive tissue overgrowth
Description	Counterintuitively, increased tumour predisposition is associated with ribosomal protein (RP) loss. Here, we provide the first evidence that RP depletion can directly drive tissue overgrowth. Haematopoietic compartment-specific knockdown (KD) of RpS19a in the Drosophila lymph gland not only results in haematopoietic stem and progenitor cell (HSPC) loss but also drives excess proliferation and tissue overgrowth. In accordance with continued ribosome assembly and protein synthesis, actively translating ribosomes (polysomes) are detected in RpS19a KD Drosophila S2 cells. The RpS19a KD ribosomes do, however, display heterogeneity and significantly altered stoichiometry of the associated translation initiation factors eIF4A and eIF5. Consistent with altered translation, in addition to increased association between polysomes and mRNA encoding growth promoting genes (e.g. Ras), we observe increased abundance of the ortholog of ribosomal (r)RNA small subunit methyltransferase NEP1. Although uncharacterised in Drosophila, in yeast and human NEP1 is implicated in methylation of 18S rRNA and, thus, 40S assembly and 80S ribosome stability. Moreover, NEP1 (EMG1) mutations in humans underpin Bowen-Conradi syndrome, a ribosomopathy associated with developmental defects, growth failure, and infantile death. Remarkably, NEP1 depletion suppresses the RpS19a KD phenotype, restoring both stem and progenitor cells and suppressing lymph gland overgrowth. We further demonstrate NEP1 depletion significantly decreases methylation of the 18S rRNA residue (Ψ1,279) that is implicated in ribosome assembly. Together, these data suggest the increased NEP1 expression associated with RpS19a KD promotes assembly of pro-proliferative “onco-ribosomes” to drive haematopoietic compartment overgrowth.
HostingRepository	PRIDE
AnnounceDate	2026-08-13
AnnouncementXML	Submission_2026-08-13_13:58:27.665.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ralf Schittenhelm
SpeciesList	scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: NEWT:7227;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-19 17:37:12	ID requested
⏵ 1	2026-08-13 13:58:28	announced

Dataset with its publication pending

submitter keyword: haematopoiesis, Drosophila,Ribosomal protein, translation

Olga Zaytseva
contact affiliation	Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, The Australian National University, Canberra
contact email	olga.zaytseva@anu.edu.au
lab head
Ralf Schittenhelm
contact affiliation	Monash University
contact email	ralf.schittenhelm@monash.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043115
     1. Label: PRIDE project
     2. Name: RpS19a depletion alters the haematopoietic translatome to directly drive tissue overgrowth