Ask about this productRelated genes to: NUDT21 antibody
- Gene:
- NUDT21 NIH gene
- Name:
- nudix hydrolase 21
- Previous symbol:
- CPSF5
- Synonyms:
- CFIM25
- Chromosome:
- 16q13
- Locus Type:
- gene with protein product
- Date approved:
- 2001-02-06
- Date modifiied:
- 2016-10-05
Related products to: NUDT21 antibody
Related articles to: NUDT21 antibody
- Targeting post-transcriptional dysregulation of tumor suppressors represents a new frontier in cancer therapy. Here, we identify the alternative polyadenylation (APA) regulator NUDT21 as a pivotal therapeutic target in oral squamous cell carcinoma (OSCC). NUDT21 is highly upregulated, correlating strongly with poor survival and advanced clinical stage. We outline a pathogenic mechanism whereby NUDT21 drives this phenotype by forcing a network of tumor suppressor transcripts, notably PTEN, into translationally-repressed, long-3'UTR isoforms. To therapeutically "re-engineer" this APA switch, we design a "Nano-APA-editor." This platform features an HMSN core with an sgRNA-NUDT21 payload and a hierarchical targeting strategy: a cancer-educated dendritic cell (DC) membrane for biomimetic camouflage and homotypic affinity, "gated" by a TA-aptamer for final precision. This system enables potent and selective NUDT21 silencing, driving a shift toward short-3'UTR isoforms. Consequently, the Nano-APA-editor effectively reinstates PTEN and associated suppressors and inhibits multiple malignant phenotypes in vitro. In an orthotopic OSCC model, it demonstrates profound tumor regression, outperforming conventional chemotherapy (PTX) with excellent biocompatibility. In vivo analysis confirmed target engagement (NUDT21-down) and functional restoration (PTEN-, WEE1-, TGF-β-up). This work validates a "post-transcriptional re-engineering" strategy, executed by a logically designed nanoplatform, as a powerful and safe modality for precision gene therapy. - Source: PubMed
Publication date: 2026/06/15
Ao YiranGu BinZhao HuiTan KunZhao QinShang Zhengjun - Alternative polyadenylation (APA) is an important mechanism of cellular stress response mediated in part by the cleavage factor Im (CFIm) complex. However, the spatiotemporal dynamics and regulatory activity of the mammalian CFIm complex during stress remain poorly understood. In this study, we determined the effect of moderate hyperosmotic stress on CFIm localization and APA profiles in HEK293 cells. Using a dual-normalization strategy that included 18S rRNA- and a CDS-based ratiometric qPCR, we identified a significant shift toward proximal polyadenylation sites (PAS) in the established CFIm targets, NUDT21 (encoding CFIm25) and DICER1. Notably, these APA dynamics displayed distinct kinetic profiles influenced by the metabolic environment: While the NUDT21 L-3'UTR/CDS ratio recovered to baseline by Day 4, DICER1 exhibited a serum-dependent response, showing a progressive decline under low-serum conditions but recovering under high-serum conditions. Crucially, these alterations were absent in non-target multi-PAS genes such as GOLGA2 and preceded any substantial reduction in total mRNA abundance, suggesting these effects represent a targeted regulatory event rather than a nonspecific byproduct of transcriptional decline. Mechanistically, hyperosmotic stress triggers a transient, coordinated redistribution of CFIm25 and CFIm68 from the nucleus to the cytoplasm, while total cellular protein concentrations remain stable. We propose that this spatial shift creates a 'stoichiometric bottleneck' within the nuclear CFIm pool, effectively limiting the processing of distal PAS. This 'stoichiometric stress response' offers a robust mechanistic framework linking subnuclear protein reorganization to the rapid reprogramming of the 3'UTR landscape, providing new insights into how cells modulate gene expression potential during osmotic adaptation. - Source: PubMed
Publication date: 2026/06/04
Soumiya HitomiOsawa MasatakeFukumitsu Hidefumi - Abnormal glycolysis plays a pivotal role in the activation of hepatic stellate cells (HSCs) and the progression of liver fibrosis, yet its regulatory mechanisms remain incompletely understood. This study aimed to investigate the role of PIM2 and its regulatory mechanisms in liver fibrosis using a CCl-induced mouse model and a TGF-β1-stimulated human HSC line (LX-2) model. The results showed that PIM2 expression was significantly upregulated in fibrotic liver tissue and a specific subset of activated HSCs. Functional experiments showed that PIM2 knockdown suppressed the activation, proliferation, and glycolysis of this specific HSC subset, whereas PIM2 overexpression promoted these processes. These effects were reversed by the glycolysis inhibitor 2-DG. Mechanistically, NUDT21 downregulation promoted PIM2 expression by regulating alternative polyadenylation (APA), resulting in PIM2 3'UTR shortening. Downstream, PIM2 activated the transcription factor CEBPB, which upregulated the transcription of the glucose transporter SLC2A1 and ultimately drove glycolysis. In line with these findings, PIM2 knockdown effectively attenuated liver fibrosis in mice. In conclusion, this study identifies PIM2 as a key driver of HSC activation and glycolysis within a distinct HSC subpopulation. PIM2 expression is regulated by NUDT21-mediated APA, and its function is mediated via the CEBPB/SLC2A1 axis, providing a potential novel therapeutic target for liver fibrosis. - Source: PubMed
Xiong MingHuang ShenanLi YangyangCai Huan - Alternative polyadenylation (APA) fine-tunes gene expression at the post-transcriptional level by generating transcript isoforms with distinct 3' untranslated region (3'UTR) lengths. Nudix hydrolase 21 (Nudt21), a core subunit of the cleavage factor Im (CFIm) complex, is a key regulator of APA; however, its function in normal hepatocytes remains poorly characterized. This study aims to elucidate the regulatory role of Nudt21 in shaping APA landscapes and gene expression in normal hepatocytes. - Source: PubMed
Publication date: 2026/05/21
Jia QiweiDai HaitaoZhang Yong - -Methyladenosine (mA) is primarily enriched in the last exons and 3' untranslated regions (3'UTRs) of messenger RNAs (mRNAs) and is associated with T cell homeostasis. Upon T cell activation, global mRNA 3'UTR shortening is facilitated through alternative polyadenylation (APA). However, it is unclear how T cells coordinate these two important posttranscriptional regulatory events to maintain quiescence. Here, we found that the mA "writer" METTL3 directly interacts with APA factor NUDT21 and guided poly(A) site selection. Deletion of in T cells resulted in simultaneous overactivation and accelerated apoptosis, leading to T cell loss and impaired adaptive immune function. Mechanistically, METTL3 recruits NUDT21 to the proximal poly(A) site of mRNA, generating long 3'UTR with mA modifications. deficiency causes 3'UTR shortening and increases expression, leading to overactivation of mammalian target of rapamycin signaling. Our study reveals an mA-guided poly(A) site selection mechanism and defines in vivo roles of mA-APA cross-talk in maintaining T cell quiescence. - Source: PubMed
Publication date: 2026/05/13
Zhang XingliLi HaixinWang GaoyangMiao ShanHao YajuanLi SongLi BinXiao HuiSu BingWu YuzhangYe YouqiongLi Hua-Bing