更新于：2024-05-01

ZC3H13

zinc finger CCCH-type containing 13

更新于：2024-05-01

基本信息

别名

DKFZp434D1812、KIAA0853、Xio

+ [3]

简介

Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs at the 3'-UTR (By similarity). Controls embryonic stem cells (ESCs) pluripotency via its role in m6A methylation (By similarity). In the WMM complex, anchors component of the MACOM subcomplex in the nucleus (By similarity). Also required for bridging WTAP to the RNA-binding component RBM15 (RBM15 or RBM15B) (By similarity).

关联

100 项与 ZC3H13 相关的临床结果

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100 项与 ZC3H13 相关的转化医学

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0 项与 ZC3H13 相关的专利（医药）

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143

项与 ZC3H13 相关的文献（医药）

2024-02-13·Cell division

Exosome-derived lncRNA A1BG-AS1 attenuates the progression of prostate cancer depending on ZC3H13-mediated m6A modification.

Article

作者: Zhi Yang ; Yu Luo ; Fan Zhang ; Likun Ma

BACKGROUND:

Exosome-derived long non-coding RNAs (lncRNAs) and N6-methyladenosine (m⁶A) modifications of lncRNAs have been shown crucial functions in prostate cancer (PCa). Herein, we aim to investigate the detailed mechanism of exosome-derived lncRNA A1BG-AS1 in PCa process.

METHODS:

PCa cell exosomes were extracted, exosomal marker proteins (CD63, CD9) were detected utilizing western blotting, and exosomes with overexpressing A1BG-AS1 were co-cultured with targeted PCa cells. qRT-PCR was used to detect A1BG-AS1 expression and m⁶A methyltransferase ZC3H13 in PCa. Transwell, colony formation and CCK-8 assays were utilized to assess the invasion, migration, and proliferation ability of PCa cells. Then, we performed actinomycin D and MeRIP assays to analyze the regulatory effect of ZC3H13 on A1BG-AS1 mRNA stability and m⁶A modification level.

RESULTS:

We observed that A1BG-AS1 and ZC3H13 expression was restricted in PCa tumors. The invasion, proliferation and migratory capacities of PCa cells could be inhibited by up-regulating A1BG-AS1 or by co-culturing with exosomes that up-regulate A1BG-AS1. Additionally, ZC3H13 promoted stable A1BG-AS1 expression by regulating the m⁶A level of A1BG-AS1.

CONCLUSION:

Exosomal A1BG-AS1 was m⁶A-modified by the m⁶A methyltransferase ZC3H13 to stabilize expression and thus prevent PCa cell malignancy. These findings offer a possible target for clinical therapy of PCa.

2024-01-30·Heliyon

Effects of N6-methyladenosine modification on metabolic reprogramming in digestive tract tumors.

Review

作者: Liang Yu ; Yuan Gao ; Qiongling Bao ; Min Xu ; Juan Lu ; Weibo Du

N6-methyladenosine (m6A), the most abundant RNA modification within cells, participates in various biological and pathological processes, including self-renewal, invasion and proliferation, drug resistance, and stem cell characteristics. The m6A methylation plays a crucial role in tumors by regulating multiple RNA processes such as transcription, processing, and translation. Three protein types are primarily involved in m6A methylation: methyltransferases (such as METTL3, METTL14, ZC3H13, and KIAA1429), demethylases (such as FTO, ALKBH5), and RNA-binding proteins (such as the family of YTHDF, YTHDC1, YTHDC2, and IGF2BPs). Various metabolic pathways are reprogrammed in digestive tumors to meet the heightened growth demands and sustain cellular functionality. Recent studies have highlighted the extensive impact of m6A on the regulation of digestive tract tumor metabolism, further modulating tumor initiation and progression. Our review aims to provide a comprehensive understanding of the expression patterns, functional roles, and regulatory mechanisms of m6A in digestive tract tumor metabolism-related molecules and pathways. The characterization of expression profiles of m6A regulatory factors and in-depth studies on m6A methylation in digestive system tumors may provide new directions for clinical prediction and innovative therapeutic interventions.

2024-01-03·Gene

The role of m⁶A modification in type 2 diabetes: a systematic review and integrative analysis.

Review

作者: Yan-Ling Li ; Yu Zhang ; Ning Chen ; Yu-Xiang Yan

This study focuses on the latest developments in the studies of m⁶A modification and provides an up-to-date summary of the association between m⁶A modification and type 2 diabetes (T2D). The possible mechanisms of m⁶A related to T2D were summarized by literature review. The differentially expressed genes (DEGs) of m⁶A methylase in T2D were analyzed from 12 datasets in Gene Expression Omnibus (GEO). The associations between m⁶A level and T2D were explored in four electronic databases, including PubMed, EmBase, Web of Science and CNKI. Standard mean difference (SMD) and 95% confidence interval (95%CI) was calculated to assess the total effect in integrative analysis. Differential expression genes detected in at least three of six tissues were ZC3H13, YTHDC1/2, and IGF2BP2. LRPPRC were differentially expressed in five tissues except in arterial tissue. A total of 6 studies were included for integrative analysis. The mean m⁶A levels were significantly lower in T2D than those in normal controls (SMD=-1.35, 95%CI: -2.58∼-0.11). This systematic review and integrative analysis summarize the previous studies on the association between m⁶A modification and T2D and the possible role of m⁶A modification in the progression of T2D, such as abnormal blood glucose, abnormal pancreatic β-cell function, insulin resistance, and abnormal lipid metabolism. The integrative analysis showed that decreased level of m⁶A was associated with T2D. These findings provide new targets for early detection and treatment for T2D.

项与 ZC3H13 相关的新闻（医药）

2024-04-06

·生物探索

Mol Cell | 中国科学院任捷/杨运桂揭示共转录m6A修饰建立机制及功能

引言N6-甲基腺苷(m6 A)是调节人类细胞多种生物过程的关键RNA修饰，但其共转录沉积和功能尚不清楚。2024年4月2日，中国科学院北京基因组研究所任捷及杨运桂共同通讯在Molecular Cell 在线发表题为“DDX21 mediates co-transcriptional RNA m6A modification to promote transcription termination and genome stability”的研究论文，该研究发现了RNA解旋酶DDX21在指导新生RNA上的m6 A修饰以进行共转录调控方面具有先前未被认识到的作用。DDX21通过识别R环与METTL3相互作用，共同募集到染色质上，当新生转录物杂交到模板DNA链上时，R环可以共同转录形成。DDX21的解旋酶活性对于METTL3介导的m6 A在新生RNA上的沉积是必需的。在转录终止区，这种联系促进了XRN2介导的RNAPII转录终止。任何这些步骤的破坏，包括DDX21、METTL3或它们的酶活性的丧失，都会导致有缺陷的终止，从而诱导DNA损伤。因此，该研究认为R-loop-DDX21-METTL3连接弥补了m6 A共转录修饰、协调转录终止和基因组稳定性的缺失环节。m6 A是哺乳动物信使RNA (mRNA)中含量最多的修饰物。它是影响mRNA整个生命周期的关键表转录组调控层，包括mRNA前剪接、3’端加工、核输出、翻译、稳定和衰变。由METTL3、METTL14、WTAP、VIRMA、HAKAI、ZC3H13和RBM15组成的甲基转移酶复合物(MTC)催化。MTC与外显子连接复合物的抑制作用一起，共同塑造了m6 A的分布轮廓，其分布在基因体上，并表现出对停止密码子的特异性富集。这种模式是在共转录过程中建立的，并在稳定状态下保持不变。尽管有这些重要的功能和已确立的模式，关于MTC如何协同转录的证据仍然很少，尽管有一些迹象体外研究已经证明了DRACH的保守基序(D = a, G或U;R = A或G;H = A, C，或U)表示MTC的酶活性。然而，这个基序很难解释其分布模式，因为只有5%的基序在体内被利用，表明在新生转录本转录过程中，存在未知的分子决定因素来决定m6 A在新生转录本上的安装。此外，它在调节转录本身中的作用已经开始被揭示，共转录安装的m6 A可能具有不同的功能，这取决于它安装的位置。然而，其安装的上游决定因素和其功能的下游效应在很大程度上仍然未知。模式图（Credit: Molecular Cell）DDX21是DEAD-box亚家族的一员，是一种多任务RNA解旋酶，它利用ATP水解产生的能量来解绕结构RNA分子，从而使下游RNA加工或RNA -蛋白复合物的重塑DDX21与各种RNA底物结合，如rRNA、snoRNA、7SK和核酸结构，包括通常由新生RNA与模板DNA杂交共同转录形成的R环。DDX21参与了广泛的生物过程，包括核糖体生物发生的多个步骤，RNA聚合酶II (RNAPII)介导的转录调节，以及表皮分化的细胞葡萄糖水平感知等。这些多面功能与许多发育缺陷和疾病(包括癌症)有关，可能反映了DDX21可能存在于多种复合物中以介导相应的细胞过程。尽管越来越多的证据表明它的重要作用，但目前还不清楚这种解旋酶是否以及如何参与决定和促进m6 A的安装。在这里。该研究发现了R-loop-DDX21-METTL3-m6 A的一个以前未知的调控轴，它通过协调募集和酶活性的联系，弥补了共转录甲基化及其调控作用的缺失环节，并协调了转录活动与基因组稳定性的关系。这个分子轴为了解m6 A在共转录调控中的基础和功能提供了重要的机制见解。切割该轴的中介结构域和关键酶活性可能为调节m6 A表转录组提供重要靶点，从而促进转录终止并维持基因组稳定性。这些发现揭示了协同转录的m6 A沉积与下游调控结果之间的相互作用，并可能有助于开发创新策略来解决与m6 A代谢失调相关的疾病。原文链接https://www.cell.com/molecular-cell/abstract/S1097-2765(24)00188-6责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

信使RNA临床1期

2023-09-13

·生物探索

阻断髓性白血病分化的新策略

N6-甲基腺苷(m6A)甲基化可通过RNA甲基转移酶复合物(MTC)沉积在染色质相关RNA (caRNAs)上，调控染色质状态和转录。然而，MTC被募集到不同基因组位点的机制仍然难以捉摸。2023年8月28日，芝加哥大学何川、陈梦洁及贝克曼研究中心陈建军共同通讯在Nature Cell Biology 在线发表题为“RBFOX2 recognizes N6-methyladenosine to suppress transcription and block myeloid leukaemia differentiation”的研究论文，该研究发现RBFOX2识别N6-甲基腺苷抑制转录，阻断髓性白血病分化。RBFOX2可以募集MTC成分RBM15，促进启动子相关RNA的甲基化。RBM15也与YTHDC1物理相互作用，将多梳抑制复合体2 (PRC2)募集到RBFOX2结合的位点，从而实现染色质沉默和转录抑制。此外，作者发现RBFOX2/m6A/RBM15/YTHDC1/PRC2轴在髓性白血病中起关键作用。下调RBFOX2显著抑制急性髓系白血病细胞的存活/增殖，促进其髓系分化。RBFOX2也是白血病干细胞/起始细胞自我更新和急性髓性白血病维持所必需的。该研究提出了m6AMTC募集和m6A沉积在caRNAs上的途径，导致位点选择性染色质调节，这对白血病具有潜在的治疗意义。m6A是哺乳动物细胞中最常见的信使RNAs。由m6A甲基转移酶复合物(MTC)安装，由METTL3/14、WTAP7、RBM15/15B8、ZC3H13和VIRMA (KIAA1429)组成，并且可以被去甲基化酶FTO11和ALKBH5去除。m6A对mRNA代谢和翻译的功能影响是通过m6A阅读蛋白介导的，例如含有YTH结构域的蛋白(YTHDC1/2)、YTHDF1/2/3。可以通过直接或间接机制优先结合m6A修饰转录本的阅读器蛋白列表，包括IGF2BP1/2/3、HNRNPA2B1、HNRNPC和HuR，还在继续扩大。虽然m6A在转录后mRNA衰变和翻译调控中的关键作用已经得到了很好的证实，但最近的研究也表明，METTL3/METTL14复合体可以介导非编码染色质相关RNAs (caRNAs)的m6A甲基化，从而调节染色质状态并调控转录；然而，MTC如何被募集到不同的染色质位点以及它如何实现位点选择调控在很大程度上是未知的。此外，YTHDC1是唯一被鉴定的m6A与染色质调控相连接的阅读蛋白。然而，如何募集YTHDC1参与m6A依赖性的位点选择性调控尚不清楚。机理模式图（图源自Nature Cell Biology）该研究展示了一个涉及MTC、YTHDC1和RNA结合蛋白(RBP) RBFOX2的转录调控轴：RBFOX2募集MTC成分RBM15来甲基化启动子相关RNAs (paRNAs)。RBM15进一步与YTHDC1相互作用，将PRC2募集到RBFOX2结合的位点进行转录抑制。RBFOX2/ m6A/RBM15/YTHDC1/PRC2轴在髓性白血病中发挥重要作用，下调RBFOX2可显著抑制急性髓性白血病(AML)细胞的存活/增殖，促进AML细胞向髓性分化。因此，RBFOX2被认为是一种染色质因子，在位点特异性染色质调节过程中促进m6A沉积在caRNAs上，具有治疗白血病的意义。综上，该研究揭示了RBFOX2作为染色质上的m6A结合蛋白在促进caRNA甲基化以抑制转录方面的功能作用。这种调控模式填补了染色质和caRNAs的m6A甲基化之间的串扰中一个关键的缺失环节。文章来源“iNture”责编|文竞择校对|文竞择End往期精选围观历史性突破！不需卵子和精子就可以合成人类胚胎热文富豪用儿子血浆“回春”科学吗？Science：血液牛磺酸缺乏驱动衰老热文世界首例！35岁的她，通过机器人操刀移植的子宫，成功诞下宝宝热文为了避免心脏骤停，53岁的他成为“第一个”植入开创性除颤器的心脏病患者热文首次披露！175家生物制药公司的薪资数据：薪资中位数达20万美元点击“阅读原文”，了解更多~

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