更新于：2024-05-01

MATR3

matrin 3

更新于：2024-05-01

基本信息

别名

KIAA0723、MATR3、matrin 3

+ [4]

简介

May play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network. In association with the SFPQ-NONO heteromer may play a role in nuclear retention of defective RNAs. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Binds to N6-methyladenosine (m6A)-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs (PubMed:32245947). May bind to specific miRNA hairpins (PubMed:28431233).

关联

100 项与 MATR3 相关的临床结果

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100 项与 MATR3 相关的转化医学

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0 项与 MATR3 相关的专利（医药）

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202

项与 MATR3 相关的文献（医药）

2024-02-10·Nature communications

Matrin3 mediates differentiation through stabilizing chromatin loop-domain interactions and YY1 mediated enhancer-promoter interactions.

Article

作者: Tianxin Liu ; Qian Zhu ; Yan Kai ; Trevor Bingham ; Stacy Wang ; Hye Ji Cha ; Stuti Mehta ; Thorsten M Schlaeger ; Guo-Cheng Yuan ; Stuart H Orkin

Although emerging evidence indicates that alterations in proteins within nuclear compartments elicit changes in chromosomal architecture and differentiation, the underlying mechanisms are not well understood. Here we investigate the direct role of the abundant nuclear complex protein Matrin3 (Matr3) in chromatin architecture and development in the context of myogenesis. Using an acute targeted protein degradation platform (dTAG-Matr3), we reveal the dynamics of development-related chromatin reorganization. High-throughput chromosome conformation capture (Hi-C) experiments revealed substantial chromatin loop rearrangements soon after Matr3 depletion. Notably, YY1 binding was detected, accompanied by the emergence of novel YY1-mediated enhancer-promoter loops, which occurred concurrently with changes in histone modifications and chromatin-level binding patterns. Changes in chromatin occupancy by Matr3 also correlated with these alterations. Overall, our results suggest that Matr3 mediates differentiation through stabilizing chromatin accessibility and chromatin loop-domain interactions, and highlight a conserved and direct role for Matr3 in maintenance of chromosomal architecture.

2024-02-06·FEBS letters

MATR3 pathogenic variants differentially impair its cryptic splicing repression function.

Article

作者: Mashiat Khan ; Xiao Xiao Lily Chen ; Michelle Dias ; Jhune Rizsan Santos ; Sukhleen Kour ; Justin You ; Rebekah van Bruggen ; Mohieldin M M Youssef ; Ying-Wooi Wan ; Zhandong Liu ; Jill A Rosenfeld ; Qiumin Tan ; Udai Bhan Pandey ; Hari Krishna Yalamanchili ; Jeehye Park

Matrin-3 (MATR3) is an RNA-binding protein implicated in neurodegenerative and neurodevelopmental diseases. However, little is known regarding the role of MATR3 in cryptic splicing within the context of functional genes and how disease-associated variants impact this function. We show that loss of MATR3 leads to cryptic exon inclusion in many transcripts. We reveal that ALS-linked S85C pathogenic variant reduces MATR3 solubility but does not impair RNA binding. In parallel, we report a novel neurodevelopmental disease-associated M548T variant, located in the RRM2 domain, which reduces protein solubility and impairs RNA binding and cryptic splicing repression functions of MATR3. Altogether, our research identifies cryptic events within functional genes and demonstrates how disease-associated variants impact MATR3 cryptic splicing repression function.

2024-01-29·Annals of clinical and translational neurology

Nationwide survey of patients with multisystem proteinopathy in Japan.

Article

作者: Satoshi Yamashita ; Yuji Takahashi ; Jun Hashimoto ; Ayuka Murakami ; Ryoichi Nakamura ; Masahisa Katsuno ; Rumiko Izumi ; Naoki Suzuki ; Hitoshi Warita ; Masashi Aoki ; Japan MSP Study Group

OBJECTIVE:

Multisystem proteinopathy (MSP) is an inherited disorder in which protein aggregates with TAR DNA-binding protein of 43 kDa form in multiple organs. Mutations in VCP, HNRNPA2B1, HNRNPA1, SQSTM1, MATR3, and ANXA11 are causative for MSP. This study aimed to conduct a nationwide epidemiological survey based on the diagnostic criteria established by the Japan MSP study group.

METHODS:

We conducted a nationwide epidemiological survey by administering primary and secondary questionnaires among 6235 specialists of the Japanese Society of Neurology.

RESULTS:

In the primary survey, 47 patients with MSP were identified. In the secondary survey of 27 patients, inclusion body myopathy was the most common initial symptom (74.1%), followed by motor neuron disease (11.1%), frontotemporal dementia (FTD, 7.4%), and Paget's disease of bone (PDB, 7.4%), with no cases of parkinsonism. Inclusion body myopathy occurred most frequently during the entire course of the disease (81.5%), followed by motor neuron disease (25.9%), PDB (18.5%), FTD (14.8%), and parkinsonism (3.7%). Laboratory findings showed a high frequency of elevated serum creatine kinase levels and abnormalities on needle electromyography, muscle histology, brain magnetic resonance imaging, and perfusion single-photon emission computed tomography.

INTERPRETATION:

The low frequency of FTD and PDB may suggest that FTD and PDB may be widely underdiagnosed and undertreated in clinical practice.

项与 MATR3 相关的新闻（医药）

2023-12-18

·今日头条

再取进展！华中科技大学学者最新发文：揭示肿瘤生物标志物和治疗靶点

本文为转化医学网原创，转载请注明出处作者：Sophia 导读：作为最突出的 RNA 修饰，N6-甲基腺苷（m6A）参与肿瘤发生和发展的调节。环状RNA（circRNA）在无处不在的生命过程中也起着至关重要的作用。肾细胞癌（RCC）的 m6A 调节是否需要 circRNA 尚不清楚。近日，华中科技大学同济医学院附属协和医院章小平和华中科技大学同济医学院基础医学院杨红枚共同通讯在期刊《Clinical and Translational Medicine》上发表题为“circRARS synergises with IGF2BP3 to regulate RNA methylation recognition to promote tumour progression in renal cell carcinoma”的研究论文，研究结果阐明了IGF2BP3/circRARS复合物在RCC进展中的致癌功能，并为RCC患者提出了新的治疗靶点。 https://onlinelibrary-wiley-com.libproxy1.nus.edu.sg/doi/full/10.1002/ctm2.1512 研究背景 01 肾细胞癌（RCC）是最常见的泌尿系统恶性肿瘤之一，全球发病率呈上升趋势。2023 年，美国预计有 81 800 例新诊断和 14 890 例 RCC 死亡。透明细胞肾细胞癌（cyncal cell carcinoma，ccRCC）是肾细胞癌最突出的病理亚型，其特点是迁移能力强，对放化疗有耐药性。大多数晚期 RCC 患者在 6-15 个月内对舒尼替尼等靶向药物产生耐药性。因此，亟需探索RCC进展的机制，并推断有效的生物标志物，以便发现RCC并预测预后。 N6-甲基腺苷（m6A）是 RNA 中最普遍的内部修饰，在各种恶性肿瘤相关途径中至关重要。然而，m6A在RCC进展中的潜在作用仍然是一个悬而未决的问题。m6A 受写入蛋白、擦除蛋白和读取蛋白的调控。其中，胰岛素样生长因子2 mRNA结合蛋白（IGF2BPs）家族是重要的读取蛋白。它们包含多个 KH 结构域，这些结构域与RNA结合并调节RNA代谢。特别是，IGF2BP3在 RCC 中显著上调，多项临床研究推荐为预后生物标志物。IGF2BP3可以识别 m6A 修饰序列，调节 mRNA 稳定性和翻译。已有研究证明，在长链非编码 RNA （lncRNA）的帮助下，IGF2BP3稳定 CDK4 mRNA 并通过 m6A 修饰驱动 RCC 发育。然而， IGF2BP3识别 m6A 修饰的潜在机制仍然被掩盖。是否有其他分子参与调控m6A识别IGF2BP3仍有待探索。研究进展 02 将稳定转染IGF2BP3 sgRNA或对照的ACHN细胞和circRARS或载体注射到4周龄裸鼠的左肾囊中，用于原位异种移植模型的构建。一致地，体内测定显示，IGF2BP3敲低减弱了 RCC 癌症干性并抑制了原位异种移植物的生长，而 circRARS 的过表达损害了抑制作用（图 7A、B ）。在原位异种移植物中，蛋白质印迹和 IHC 测定显示 CAPN15、CD44、HMGA2、TNRC6A 和 ZMIZ2 的蛋白水平受 IGF2BP3/circRARS 复合物的调节（图 7C）。IF显示IGF2BP3/circRARS复合物促进RCC细胞增殖。Ki67 是细胞增殖的生物标志物，PAX8 阳性代表 RCC 细胞（图 7D）。静脉尾部肿瘤注射试验表明，敲低IGF2BP3可减少肺转移，而circRARS的过表达可促进肺转移（图7E）。裸鼠肺上的H&E染色表明IGF2BP3/circRARS复合物促进了RCC肺转移的形成和增殖（图7F，G）。最后，IGF2BP3的过表达可以缩短裸鼠的存活时间，这可以通过circRARS敲低来挽救（图7H）。综上所述， IGF2BP3/circRARS 复合物在 RCC 中的致癌特性在体内得到了验证。 IGF2BP3/circRARS 复合物促进体内 RCC 进展研究结果 03 本研究，荟萃分析和生物信息学发现，IGF2BP3在 RCC 中上调，表明预后较差。IGF2BP3在体外和体内显著促进了RCC的进展。从机制上讲，circRARS 与 KH1–KH2 结构域的 IGF2BP3 结合以增强 m6A 修饰识别。12-nt序列（GUCUUCCAGCAA）被证明是circRARS的IGF2BP3结合位点。此外，CAPN15、CD44、HMGA2、TNRC6A 和 ZMIZ2 被筛选为 IGF2BP3/circRARS 复合物以 m6A 依赖性方式调控的靶基因。circRARS募集了稳定蛋白，包括HuR、Matrin3和pAbPC1，从而提高了上述5个靶基因的mRNA稳定性。因此，IGF2BP3/circRARS 复合物促进了 RCC 细胞的脂质积累，并通过靶基因促进了舒尼替尼耐药性。circRARS 与 IGF2BP3 协同促进 m6A 识别，从而促进 RCC 进展。因此，IGF2BP3可能是 RCC 诊断和预后的潜在生物标志物以及治疗靶点。参考资料： https://onlinelibrary-wiley-com.libproxy1.nus.edu.sg/doi/full/10.1002/ctm2.1512 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 北京｜12月19日-20日 ▶第四届单细胞测序技术应用研讨会暨单细胞&空间组学研讨会（日程稍后公布）点击对应文字查看详情

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