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更新于：2025-05-07

NUDT21

更新于：2025-05-07

基本信息

别名

CFIM25、Cleavage and polyadenylation specificity factor 25 kDa subunit、Cleavage and polyadenylation specificity factor subunit 5

+ [9]

简介

Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs (PubMed:14690600, PubMed:15937220, PubMed:17024186, PubMed:17098938, PubMed:29276085, PubMed:8626397, PubMed:9659921). CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals) (PubMed:14690600, PubMed:17024186, PubMed:8626397, PubMed:9659921). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation (PubMed:17098938, PubMed:23187700, PubMed:29276085). The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs (PubMed:17098938, PubMed:20695905, PubMed:29276085). NUDT21/CPSF5 activates indirectly the mRNA 3'-processing machinery by recruiting CPSF6 and/or CPSF7 (PubMed:29276085). Binds to 5'-UGUA-3' elements localized upstream of pA signals that act as enhancers of pre-mRNA 3'-end processing (PubMed:14690600, PubMed:15169763, PubMed:17024186, PubMed:20479262, PubMed:22813749, PubMed:8626397). The homodimer mediates simultaneous sequence-specific recognition of two 5'-UGUA-3' elements within the pre-mRNA (PubMed:20479262, PubMed:21295486). Plays a role in somatic cell fate transitions and pluripotency by regulating widespread changes in gene expression through an APA-dependent function (By similarity). Binds to chromatin (By similarity). Binds to, but does not hydrolyze mono- and di-adenosine nucleotides (PubMed:18445629).

关联

靶点

NUDT21

作用机制

NUDT21 inhibitors

在研机构

复旦大学附属眼耳鼻喉科医院

原研机构

复旦大学附属眼耳鼻喉科医院

在研适应症

视网膜母细胞瘤

非在研适应症-

最高研发阶段早期临床1期

首次获批国家/地区-

首次获批日期1800-01-20

项与 NUDT21 相关的临床试验

NCT06424301

/ Recruiting早期临床1期IIT

Targeting NUDT21 siRNA Drugs for Patients With Refractory Retinoblastoma (A Two-center Prospective Single Arm Trial)

Retinoblastoma (RB) is the most common intraocular malignancy in children and accounts for 11% of all cancers in children under the age of 1 year. Although the incidence of RB is low, approximately 1/15,000
1/20,000, it tends to metastasize to the intracranial area through the optic nerve pathway leading to poor prognosis for patients with RB. Currently, with the emergence of new administration routes, such as intravitreal and intrarterial chemotherapy, the rate of eye preservation has been effectively improved. However, the use of high doses of chemotherapeutic agents may lead to visual impairments due to long-term retinal toxicity and some tumors recur or become resistant to chemotherapeutic agents after treatment. In such cases, ocular resection is the only option to prevent extraocular metastasis and death.
Therefore, studies on retinoblastoma are currently focused on finding new targeted therapies to increase anti-tumor activity and reduce side effects. In this study, a novel targeting NUDT21 siRNA drug will be used to treat patients with refractory retinoblastoma. This drug promotes tumor apoptosis by regulating the 3'UTR plus tail of SMC1A, which makes the proliferative activity of tumor cells weaken and achieves tumor control. At the same time, since the targeted drug only focuses on tumor cells, it has reduced side effects compared with existing local chemotherapy regimens.
Based on the above background, this study will explore the feasibility and effectiveness of intravitreal injection of NUDT21 siRNA in patients with refractory retinoblastoma through a two-center prospective study.

开始日期2024-12-20

申办/合作机构

复旦大学附属眼耳鼻喉科医院

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100 项与 NUDT21 相关的临床结果

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100 项与 NUDT21 相关的转化医学

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0 项与 NUDT21 相关的专利（医药）

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120

项与 NUDT21 相关的文献（医药）

2025-03-20·Nucleic Acids Research

N4-acetylcytidine coordinates with NP1 and CPSF5 to facilitate alternative RNA processing during the replication of minute virus of canines

Article

作者: Liu, Yi ; Liu, Haibin ; Guan, Wuxiang ; Qin, Shuangkang ; Zhang, Xueyan ; Wang, Jun ; Hao, Haojie ; Ding, Shuang ; Chen, Zhen ; Liu, Lishi ; Huang, Fang ; Liu, Haizhou ; Yu, Baocheng

AbstractRNA modifications play crucial roles in RNA metabolism, structure, and functions. N4-acetylcytidine (ac4C) modifications have been shown to enhance stability and translation efficiency of messenger RNAs and viral RNAs. However, the relationship between ac4C and alternative RNA processing remains unexplored. Here, N-acetyltransferase 10 (NAT10) and its catalyzed ac4C modifications on minute virus of canines (MVC) were shown to regulate viral DNA replication and RNA processing, including both the alternative RNA splicing and polyadenylation. Through acRIP-seq and RedaC:T-seq, functional ac4C-modified residue 3311 was identified and characterized, which affected MVC RNA processing rather than altered the viral RNA stability. Ac4C modification at nt 3311 was revealed to participate in NP1-mediated viral RNA processing without influencing RNA affinity of NP1. Meanwhile, CPSF5 was identified to interact with NP1 and mediate viral RNA processing in an ac4C-dependent manner. Further in vitro assays showed that NP1 recruited CPSF5 to MVC RNAs, and the ac4C modification promoted specific binding of CPSF5 to the target region, which ensured precise alternative MVC RNA processing. This study not only reveals the functions of NAT10 and ac4C but also elucidates the mechanisms by which RNA modifications orchestrate MVC proteins and host factors for efficient viral replication and alternative RNA processing.

2025-03-01·Biochemical and Biophysical Research Communications

Discovery of myeloid zinc finger (MZF) 1 nuclear bodies

Article

作者: Calderwood, Stuart K ; Eguchi, Takanori

Myeloid zinc finger 1 (MZF1) is a multifaceted transcription factor that can act either as a transcriptional activator or a gene repressor. We examined its production of nuclear bodies (NBs) and subcellular localization. Proteomic and protein-protein interaction analysis were used to identify its cofactors and interactions. These revealed the presence of MZF1-NBs (intranuclear oligomers containing MZF1). MZF-NBs are similar to some other nuclear bodies, notably promyelocytic leukemia (PML) -NBs in terms of size and morphology. However the two structures appear to be different. MZF-NBs and PML-NBs were found to associate in the nucleus. Both MZF1 and PML are SUMO1-SUMOylated in PC-3 cells. Sumoylated MZF1 can interact with proteins containing SUMO-interaction motifs (SIM) through SUMO-SIM interaction. Interactome analysis revealed that its NBs participate in the stress response (TPR and UBAP2L), protein folding (CALR and ANKRD40), transcription, post-translational modification (TRIM33, ACOT7, CAMK2D, and CAMK2G), and RNA binding (ALURBP and CPSF5).

2025-01-31·The FASEB Journal

Characterization and molecular targeting of CFIm25 (NUDT21/CPSF5) mRNA using miRNAs

Article

作者: Gupta, Mahesh ; Masamha, Chioniso Patience ; Khan, Naazneen

AbstractChanges in protein levels of the mammalian cleavage factor, CFIm25, play a role in regulating pathological processes including neural dysfunction, fibrosis, and tumorigenesis. However, despite these effects, little is known about how CFIm25 (NUDT21) expression is regulated at the RNA level. A potential regulator of NUDT21 mRNA are small non‐coding microRNAs (miRNAs). In general, miRNAs bind to the 3′untranslated regions (3′UTRs) and can target the bound mRNA for degradation or inhibit translation thus affecting the levels of protein in cells. Interestingly, a mechanism known as alternative polyadenylation (APA) enables mRNAs to escape miRNA regulation by generating mRNAs with 3′UTRs of different sizes. As many miRNA target sites are located within the 3′UTR, shortening the 3′UTR allows mRNAs to evade miRNAs targeting this region. The differences in the lengths and the sequence composition of the 3′UTRs may also impact the mRNA's translatability and subcellular localization. APA has been reported to regulate over 70% of protein coding genes, thus increasing the transcript repertoire. Several proteins, including mammalian cleavage factor, CFIm25 (NUDT21), have been shown to regulate APA. In this study we wanted to determine whether CFIm25 (NUDT21), itself a regulator of APA, undergoes APA to evade miRNA regulation. We used the blood cancer mantle cell lymphoma (MCL) cells as a model and showed that in these cells, NUDT21 is relatively stable with a long half‐life. In addition, the NUDT21 pre‐mRNA undergoes alternative APA within the same terminal exon. The three different sized NUDT21 mRNAs have different 3′UTR lengths and they each use a different canonical polyadenylation signal, AAUAAA, for 3′end cleavage and polyadenylation. Use of miRNA mimics and inhibitors showed that miR‐23a, miR‐222, and miR‐323a play a significant role in regulating NUDT21 expression. Hence, these results suggest that NUDT21 mRNA is stable and the different 3′UTRs generated through APA of NUDT21 play an important role in evading miRNA regulation and offers insights into how levels of CFIm25 (NUDT21) may be fine‐tuned as needed under different physiological and pathological conditions.

项与 NUDT21 相关的新闻（医药）

2025-04-29

·今日头条

最全面研究！华科大&武大团队破解肺癌防治密码，精准干预新时代来临

【导读】新出现的证据强调了APA在基因转录后调控中的关键作用，与 APA 相关的遗传变异（apaQTLs）对多种疾病具有特别重要的意义。然而，APA 的遗传调控及其在非小细胞肺癌（NSCLC）风险中的作用尚未得到充分研究。 4月26日，华中科技大学/企业订阅用户研究人员合作共同在期刊《Advanced Science》上发表了研究论文，题为“Genetic Regulation of Alternative Polyadenylation Provides Novel Insights into Molecular Mechanisms Underlying Non-small Cell Lung Cancer”，本研究中，研究人员通过利用来自癌症基因组图谱的基因型和 APA 数据，在非小细胞肺癌样本中确定了遗传变异与 APA 之间的关联。值得注意的是，将 apaQTL 变异与传统 GWAS 衍生的 PRS 集成被证明是筛查非小细胞肺癌的潜在工具。从机制上讲，rs9606 通过等位基因特异性与 NUDT21 相互作用诱导 LYRM4 的异常 APA 过程，从而导致癌基因 LYRM4 表达增加，进而增加非小细胞肺癌风险。本研究证明了与 APA 相关的遗传变异在非小细胞肺癌风险中的独特贡献，为非小细胞肺癌的病因学和临床干预提供了关键线索和潜在靶点。 https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202502008 背景知识 01 肺癌仍是全球最常见的癌症之一，也是癌症相关死亡的首要原因，对人类健康构成严重威胁。非小细胞肺癌（NSCLC）是最常见的类型，占所有肺癌病例的 85%。众所周知，除了环境风险因素（如吸烟）外，基因变异也会增加患非小细胞肺癌的风险。GWAS已确定了众多与非小细胞肺癌风险相关的基因变异，但确定因果变异并阐明其功能机制仍是一项持续的挑战。据估计，近 70% 的人类基因具有多个多聚腺苷酸化位点，会发生 APA。通过使用不同的多聚（A）位点，APA 会产生具有不同 3'非翻译区（UTR）长度的转录本。由于 3'UTR 包含 RNA 结合蛋白（RBP）和 miRNA 的调节元件，APA 可通过改变 mRNA 稳定性、翻译效率或蛋白质的细胞定位来调节基因表达。已知 APA 在癌症中显著失调。异常 APA 是多种癌症的常见特征，并导致癌基因和肿瘤抑制基因的失调。此外，关键 APA 调节因子的表达改变通常会全局改变 APA，并扰乱与癌症相关的生物过程，包括细胞周期、细胞凋亡和增殖。尽管有这些观察结果，但研究人员对诱导异常 APA 的潜在机制仍知之甚少。 apaQTLs 目标基因在癌症发展和治疗中发挥关键作用 02 根据apaQTL 分析，研究人员共鉴定出 2037 个基因和 2109 个相关的 APA 事件。研究人员首先对 aGenes 进行了通路富集分析。研究人员接下来基于 TCGA 的数据评估了 NSCLC 中的 SCNA。鉴于免疫细胞在调节癌症发展中的新兴作用，研究人员进一步评估了它们与 aGene 表达的关联，其中免疫细胞浸润数据使用 TIMER 和 EPIC 算法进行量化。结果表明，多个 aGenes与特定的免疫细胞亚群相关，包括 CD8+T 细胞、CD4+T 细胞和巨噬细胞。为了了解 aGenes对药物反应的影响，研究人员利用GDSC数据进行了系统的药物基因组学分析，共鉴定出 34902 个显著相关的 aGenes - 药物配对。研究人员重点关注与 aGenes高度相关的药物及其药物靶点。值得注意的是，排名靠前的药物类别是靶向 ERK/MAPK 信号通路的药物，包括曲美替尼和达拉非尼，这两种药物已获美国食品药品监督管理局（FDA）批准联合用于非小细胞肺癌（NSCLC）的治疗。综上所述，上述分析结果表明 apaQTLs 目标基因在癌症发展和治疗中具有独特的作用。结论 03 本研究发现可能有助于增进对基因变异与非小细胞肺癌易感性之间分子机制的理解，并最终改善非小细胞肺癌的精准预防和治疗策略。参考资料： https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202502008 【关于投稿】转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。责任声明：本稿件如有错误之处，敬请联系转化医学网客服进行修改事宜！微信号：zhuanhuayixue 热门推荐活动点击免费报名 🕓 浙江｜2025年5月9日 ▶ 首届精准医学国际学术研讨会暨队列研究先锋计划颁奖仪式 🕓 上海｜2025年6月12-15日 ▶ 第七届上海国际癌症大会暨第十八届全国医学生物技术研讨会暨第六届中德双边论坛 🕓 上海｜2025年7月17-18日 ▶ 第四届长三角体外诊断产业高峰论坛 🕓 北京｜2025年9月19-20日 ▶ 第六届单细胞技术应用研讨会暨空间组学前沿研讨会 🕓 上海｜2025年11月14-15日 ▶ 第二届中国类器官转化医学大会点击对应文字查看详情

临床研究信使RNA