NUDT21 CUT&Tag in neuroblastoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE312399 | GEO | 2026/07/01
REPOSITORIES: GEO
Similar Datasets
Project description:Alternative polyadenylation (APA) generates mRNAs with distinct 3′-untranslated regions (3′ UTRs) to regulate post-transcriptional gene expression and is critical in many tumors. However, the role of alternative 3′ UTRs in neurolastoma (NB) remains elusive. Here, we show that NUDT21 knockdown inhibits NB cell proliferation, induces cycle arrest/apoptosis in vitro, and suppresses xenograft growth in nude mice. Mechanistically, NUDT21 silencing triggers global APA dynamics, with ∼85% of APA genes switching to proximal poly(A) sites, shortening 3′ UTRs. Integrative PAS-seq/RNA-seq analyses reveal that NUDT21 regulates E2F targets (e.g., MKI67) via APA. Additionally, NUDT21 occupies gene regulatory regions to directly activate E2F target transcription. Our findings demonstrate NUDT21 sustains NB proliferation through dual APA-dependent and APA-independent mechanisms, highlighting targeting NUDT21 or its downstream pathways as a promising therapeutic strategy.
2026-07-01 | GSE311302 | GEO
Project description:Alternative polyadenylation (APA) generates mRNAs with distinct 3′-untranslated regions (3′ UTRs) to regulate post-transcriptional gene expression and is critical in many tumors. However, the role of alternative 3′ UTRs in neurolastoma (NB) remains elusive. Here, we show that NUDT21 knockdown inhibits NB cell proliferation, induces cycle arrest/apoptosis in vitro, and suppresses xenograft growth in nude mice. Mechanistically, NUDT21 silencing triggers global APA dynamics, with ∼85% of APA genes switching to proximal poly(A) sites, shortening 3′ UTRs. Integrative PAS-seq/RNA-seq analyses reveal that NUDT21 regulates E2F targets (e.g., MKI67) via APA. Additionally, NUDT21 occupies gene regulatory regions to directly activate E2F target transcription. Our findings demonstrate NUDT21 sustains NB proliferation through dual APA-dependent and APA-independent mechanisms, highlighting targeting NUDT21 or its downstream pathways as a promising therapeutic strategy.
2026-07-01 | GSE311299 | GEO
Project description:Alternative polyadenylation (APA) is a widespread post-transcriptional mechanism that regulates transcript stability, localization, and translation. While dysregulated APA has been implicated in multiple cancers, its role in T-cell acute lymphoblastic leukemia (T-ALL) remains poorly understood. Here, we identify NUDT21, a core subunit of the APA machinery, as an essential oncogenic regulator in T-ALL. NUDT21 is significantly upregulated in T-ALL patient samples and associated with poor prognosis. Functional assays demonstrate that NUDT21 knockdown inhibits T-ALL cell proliferation, induces apoptosis, and suppresses leukemia progression in vivo. Integrative PAS-seq and RNA-seq analysis reveals that NUDT21 maintains distal polyadenylation site usage of oncogenic transcripts, including UBE2D3, whose 3′UTR shortening upon NUDT21 loss leads to decreased expression and impaired leukemic cell growth. In addition to its APA role, NUDT21 occupies gene regulatory regions and directly activates transcriptional programs enriched for MYC and E2F targets, promoting cell cycle progression and ribosome biogenesis. Pharmacological suppression of NUDT21 using ouabain, a cardiac glycoside, downregulates UBE2D3 and E2F/MYC effectors, resulting in robust anti-leukemic effects.Our findings reveal a dual regulatory role of NUDT21 in T-ALL, functioning through both APA-dependent and APA-independent mechanisms to sustain leukemic proliferation. Targeting NUDT21 or its downstream programs represents a promising therapeutic strategy for T-ALL.
2026-02-01 | GSE305440 | GEO
Project description:Alternative polyadenylation (APA) is a widespread post-transcriptional mechanism that regulates transcript stability, localization, and translation. While dysregulated APA has been implicated in multiple cancers, its role in T-cell acute lymphoblastic leukemia (T-ALL) remains poorly understood. Here, we identify NUDT21, a core subunit of the APA machinery, as an essential oncogenic regulator in T-ALL. NUDT21 is significantly upregulated in T-ALL patient samples and associated with poor prognosis. Functional assays demonstrate that NUDT21 knockdown inhibits T-ALL cell proliferation, induces apoptosis, and suppresses leukemia progression in vivo. Integrative PAS-seq and RNA-seq analysis reveals that NUDT21 maintains distal polyadenylation site usage of oncogenic transcripts, including UBE2D3, whose 3′UTR shortening upon NUDT21 loss leads to decreased expression and impaired leukemic cell growth. In addition to its APA role, NUDT21 occupies gene regulatory regions and directly activates transcriptional programs enriched for MYC and E2F targets, promoting cell cycle progression and ribosome biogenesis. Pharmacological suppression of NUDT21 using ouabain, a cardiac glycoside, downregulates UBE2D3 and E2F/MYC effectors, resulting in robust anti-leukemic effects.Our findings reveal a dual regulatory role of NUDT21 in T-ALL, functioning through both APA-dependent and APA-independent mechanisms to sustain leukemic proliferation. Targeting NUDT21 or its downstream programs represents a promising therapeutic strategy for T-ALL.
2026-02-01 | GSE305438 | GEO
Project description:Alternative polyadenylation (APA) is a widespread post-transcriptional mechanism that regulates transcript stability, localization, and translation. While dysregulated APA has been implicated in multiple cancers, its role in T-cell acute lymphoblastic leukemia (T-ALL) remains poorly understood. Here, we identify NUDT21, a core subunit of the APA machinery, as an essential oncogenic regulator in T-ALL. NUDT21 is significantly upregulated in T-ALL patient samples and associated with poor prognosis. Functional assays demonstrate that NUDT21 knockdown inhibits T-ALL cell proliferation, induces apoptosis, and suppresses leukemia progression in vivo. Integrative PAS-seq and RNA-seq analysis reveals that NUDT21 maintains distal polyadenylation site usage of oncogenic transcripts, including UBE2D3, whose 3′UTR shortening upon NUDT21 loss leads to decreased expression and impaired leukemic cell growth. In addition to its APA role, NUDT21 occupies gene regulatory regions and directly activates transcriptional programs enriched for MYC and E2F targets, promoting cell cycle progression and ribosome biogenesis. Pharmacological suppression of NUDT21 using ouabain, a cardiac glycoside, downregulates UBE2D3 and E2F/MYC effectors, resulting in robust anti-leukemic effects.Our findings reveal a dual regulatory role of NUDT21 in T-ALL, functioning through both APA-dependent and APA-independent mechanisms to sustain leukemic proliferation. Targeting NUDT21 or its downstream programs represents a promising therapeutic strategy for T-ALL.
2026-02-01 | GSE305852 | GEO
Project description:Alternative polyadenylation (APA) is a widespread post-transcriptional mechanism that regulates transcript stability, localization, and translation. While dysregulated APA has been implicated in multiple cancers, its role in T-cell acute lymphoblastic leukemia (T-ALL) remains poorly understood. Here, we identify NUDT21, a core subunit of the APA machinery, as an essential oncogenic regulator in T-ALL. NUDT21 is significantly upregulated in T-ALL patient samples and associated with poor prognosis. Functional assays demonstrate that NUDT21 knockdown inhibits T-ALL cell proliferation, induces apoptosis, and suppresses leukemia progression in vivo. Integrative PAS-seq and RNA-seq analysis reveals that NUDT21 maintains distal polyadenylation site usage of oncogenic transcripts, including UBE2D3, whose 3′UTR shortening upon NUDT21 loss leads to decreased expression and impaired leukemic cell growth. In addition to its APA role, NUDT21 occupies gene regulatory regions and directly activates transcriptional programs enriched for MYC and E2F targets, promoting cell cycle progression and ribosome biogenesis. Pharmacological suppression of NUDT21 using ouabain, a cardiac glycoside, downregulates UBE2D3 and E2F/MYC effectors, resulting in robust anti-leukemic effects.Our findings reveal a dual regulatory role of NUDT21 in T-ALL, functioning through both APA-dependent and APA-independent mechanisms to sustain leukemic proliferation. Targeting NUDT21 or its downstream programs represents a promising therapeutic strategy for T-ALL.
2026-02-01 | GSE305851 | GEO
Project description:Defining the molecular mechanisms governing macrophage-driven inflammation is essential for developing targeted interventions for ARDS. One such mechanism could be alternative polyadenylation (APA), a post-transcriptional regulatory process that plays a critical role in gene regulation. Most mammalian genes, including key proinflammatory mediators, contain multiple polyadenylation sites (PAS). APA regulates the addition of poly(A) tails at alternative PAS, generating transcripts with different 3' UTR lengths. One key regulator of APA is Nudix Hydrolase 21 (NUDT21), a critical cleavage factor Im (CFIm) component. However, whether NUDT21-mediated APA plays a role in inflammation during ARDS is not known. Thus, the goal of this study is to identify the APA genes regulated by NUDT21 in macrophages.
2025-08-11 | GSE292996 | GEO
Project description:Stem cells continually self-renew and differentiate to sustain tissue homeostasis, yet the role of post-transcriptional mechanisms in guiding these processes remains incompletely understood. Here, we demonstrate that the regulation of 3’UTR length via alternative mRNA polyadenylation (APA) is essential for stem cell function across diverse tissues. Modulating the APA regulator Nudt21 reveals that stem cell self-renewal and differentiation depend on distinct dosage thresholds and thus can be uncoupled. Specifically, moderate Nudt21 suppression elicits a maturation arrest of stem cells due to 3’UTR-shortening of differentiation-associated mRNAs that escape miRNA regulation and perturb ceRNA networks. By contrast, complete Nudt21 suppression additionally shortens the 3’UTRs of mRNAs encoding essential multiprotein complexes, including the nuclear pore, leading to complex destabilization, proteotoxic stress, DNA damage, and cell cycle arrest. Critically, deletion of the alternative 3’UTRs of individual nucleoporins recapitulates defects observed with Nudt21 loss. We further demonstrate that the co-translational assembly of dozens of protein complexes is impaired in Nudt21-deficient cells, providing a mechanistic framework for compromised complex integrity. Collectively, our results show that APA plays distinct, dose-dependent roles in stem cell homeostasis by fine-tuning the expression of differentiation-associated genes and coordinating the biogenesis of multiprotein complexes essential for cell cycle progression.
2025-11-21 | GSE280706 | GEO
Project description:HCC is the third leading cause of cancer-related deaths worldwide. However, the molecular mechanisms underlying the progression of HCC is still largely elusive. NUDT21 (CFIm25) is an important mediator of 3′ UTR APA and demonstrates a causal relationship between alternative polyadenylation and cancer cell proliferation. Although the function of NUDT21 has been explored in glioblastoma tumor, the functional significance of NUDT21 in solid tumors is not well understood. In this study, we observed that NUDT21 is suppressed in human HCC tissues, compared to adjacent noncancerous tissues. In addition we found that the HCC patients with suppressed NUDT21 are statistically associated with poor outcomes. These observations suggest NUDT21 possibly functions as tumor suppressor in hepatocellular carcinoma (HCC).
2018-01-25 | E-MTAB-6368 | biostudies-arrayexpress
Project description:Alternative polyadenylation modulates gene expresion via changing the length of 3'UTR. Among the complexes involving in APA, CFIm complex plays a central role in determining the usage of proximal PAS versus distal one. NUDT21, also named as CFIm25 and CPSF5, is the core component of CFIm complex. To date, except CPSF6 and CPSF7, there are few proteins reported to interact with NUDT21. In this project, the interactome of NUDT21 was identified by IP-MS.
2022-01-21 | PXD031134 |