Dataset Information

Loss of Drosophila nucleostemin 1 disrupts ribosomal protein homeostasis and rRNA processing to trigger apoptosis via the Xrp1/Irbp18 complex

ABSTRACT: In this study, we investigate the role of Ns1 in proliferating epithelial tissues using the Drosophila wing imaginal disc as a model. We demonstrate that knocking down Ns1 in wing discs leads to strong apoptosis. However, unlike the reported effect on overexpressed RPs, we did not observe nucleolar accumulation of endogenous RPs upon Ns1 knockdown. Instead, proteomic analysis and the following validation with Western blotting and immunostaining reveal that Ns1 deficiency reduces the protein levels of most RPs without affecting their transcription or proteasomal degradation. We further demonstrate that loss of Ns1 upregulates the Xrp1/Irbp18 complex, which subsequently induces apoptosis through activating JNK and suppresses translation through a JNK-independent mechanism

ORGANISM(S): Drosophila Melanogaster

SUBMITTER: Gongping Sun

PROVIDER: PXD075076 | iProX | Mon Mar 02 00:00:00 GMT 2026

REPOSITORIES: iProX

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Loss of Drosophila nucleostemin 1 disrupts ribosomal protein homeostasis and rRNA processing to trigger apoptosis via the Xrp1/Irbp18 complex.

Liu Xiuxiu X Hou Min M Zhang Yuanyuan Y Liu Huan H Li Xiaojiao X Su Yuanlin Y Ding Huiyuan H Gong Yanqin Y Liu Qiao Q Gong Yaoqin Y Sun Gongping G

Cell death discovery 20260614 1

Ribosome biogenesis, a process of producing ribosomes, plays an essential role in cell survival, proliferation and apoptosis. Nucleostemin (NS) is a conserved nucleolar protein highly expressed in proliferating cells but markedly reduced in differentiated cells. Previous studies on mammalian systems have shown that loss of NS triggers p53-dependent apoptosis and impairs ribosomal RNA (rRNA) processing. In this study, using the Drosophila wing imaginal disc, which is a proliferating epithelial ti ...[more]

PMID: 42288481

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Project description:A significant percentage of HIV-infected individuals experience a sharp decline in CD4+ T cell counts and progress to AIDS quickly after primary infection. Identification of biomarkers distinguishing rapid progressors (RPs) versus chronic progressors (CPs) is critical for early clinical intervention and could provide novel strategies to facilitate vaccine design and immune therapy. mRNA and miRNA expression profiles in the peripheral blood mononuclear cells (PBMCs) of RPs and CPs were investigated at 111±22 days (Mean±SD) of HIV infection. The association of mRNA and miRNA expression with disease progression was examined by receiver operating characteristic analysis and Kaplan-Meier survival analysis. Pathway enrichment analysis showed that genes with deregulated expression in RPs are primarily involved in apoptosis pathways. Furthermore, we found that 5 miRNAs (miR-31, -200c, -526a, -99a and -503) in RPs were significantly decreased compared to those in CPs (P<0.05). The decreased expression of these miRNAs was associated with rapid disease progression of HIV infection with a 94% predictive value as measured by the area under the curve. The upregulated predicted targets from the 5 signature miRNAs and all upregulated genes identified from mRNA microarray converged to the apoptosis pathway. Moreover, overexpression of miR-31 in primary human T cells promoted their survival. Our results have identified a distinct transcriptomic signature in PBMCs of RPs and provided novel insights to the pathogenesis of HIV infection. The initial 347 miRNA array was performed in 11 RPs, 6 CPs and 4 corresponding matched normal controls (training group); and only the miRNAs differentially expressed between RPs and CPs (P<0.05) in training group were detected in a subsequent validation group (19 RPs versus 10 CPs). miRNAs differentially expressed in 17 early HIV infected patients (including 11 RPs and 6 CPs) and 4 healthy controls in training cohort were firstly identified. Then, miRNAs differed RPs from CPs were compared in both training and validation cohort.

Dataset Information

Loss of Drosophila nucleostemin 1 disrupts ribosomal protein homeostasis and rRNA processing to trigger apoptosis via the Xrp1/Irbp18 complex

Publications

Loss of Drosophila nucleostemin 1 disrupts ribosomal protein homeostasis and rRNA processing to trigger apoptosis via the Xrp1/Irbp18 complex.

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