更新于：2024-05-01

RBM15

RNA binding motif protein 15

更新于：2024-05-01

基本信息

别名

One-twenty two protein 1、OTT、OTT1

+ [4]

简介

RNA-binding protein that acts as a key regulator of N6-methyladenosine (m6A) methylation of RNAs, thereby regulating different processes, such as hematopoietic cell homeostasis, alternative splicing of mRNAs and X chromosome inactivation mediated by Xist RNA (PubMed:27602518). 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 (By similarity). Plays a key role in m6A methylation, possibly by binding target RNAs and recruiting the WMM complex (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: acts by binding Xist RNA and recruiting the WMM complex, which mediates m6A methylation, leading to target YTHDC1 reader on Xist RNA and promoting transcription repression activity of Xist (PubMed:27602518). Required for the development of multiple tissues, such as the maintenance of the homeostasis of long-term hematopoietic stem cells and for megakaryocyte (MK) and B-cell differentiation (By similarity). Regulates megakaryocyte differentiation by regulating alternative splicing of genes important for megakaryocyte differentiation; probably regulates alternative splicing via m6A regulation (PubMed:26575292). Required for placental vascular branching morphogenesis and embryonic development of the heart and spleen (By similarity). Acts as a regulator of thrombopoietin response in hematopoietic stem cells by regulating alternative splicing of MPL (By similarity). May also function as an mRNA export factor, stimulating export and expression of RTE-containing mRNAs which are present in many retrotransposons that require to be exported prior to splicing (PubMed:17001072, PubMed:19786495). High affinity binding of pre-mRNA to RBM15 may allow targeting of the mRNP to the export helicase DBP5 in a manner that is independent of splicing-mediated NXF1 deposition, resulting in export prior to splicing (PubMed:17001072, PubMed:19786495). May be implicated in HOX gene regulation (PubMed:11344311).

关联

100 项与 RBM15 相关的临床结果

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100 项与 RBM15 相关的转化医学

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0 项与 RBM15 相关的专利（医药）

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251

项与 RBM15 相关的文献（医药）

2024-02-20·Virchows Archiv : an international journal of pathology

Myeloid sarcoma with RBM15::MRTFA (MKL1) mimicking vascular neoplasm.

Article

作者: Fatma Gündoğdu ; Abbas Agaimy ; Selin Aytaç ; Volkan Hazar ; Ayşegül Üner ; Kemal Kösemehmetoğlu

Extramedullary involvement of acute myeloid leukemia (AML), aka myeloid sarcoma, is a rare phenomenon in acute megakaryoblastic leukemia with RBM15:: MRTFA(MKL1) fusion, which might mimic non-hematologic malignancies. A 7-month-old infant presented with leukocytosis, hepatosplenomegaly, multiple lymphadenopathies, and a solid mass in the right thigh. Initially, the patient was diagnosed with a malignant vascular tumor regarding the expression of vascular markers from the biopsy of the right thigh lesion that was performed after the inconclusive bone marrow biopsy. The second bone marrow biopsy, which was performed due to the partial response to sarcoma treatment, showed hypercellular bone marrow with CD34 and CD61-positive spindle cell infiltration and > 20% basophilic blasts with cytoplasmic blebs. RNA sequencing of soft tissue biopsy revealed the presence of RBM15::MRTFA(MKL1) fusion. Based on these findings, myeloid sarcoma/AML with RBM15::MRTFA(MKL1) fusion diagnosis was made. AML with RBM15::MRTFA(MKL1) fusion can initially present as extramedullary lesions and might cause misdiagnosis of non-hematologic malignancies.

2024-01-30·Heliyon

The RNA m6A writer RBM15 contributes to the progression of esophageal squamous cell carcinoma by regulating miR-3605-5p/KRT4 pathway.

Article

作者: Huan Wang

Cancer progression can be modulated by N6-methyladenosine (m6A) modification. RNA binding motif protein 15 (RBM15) is an essential RNA m6A writer that influences carcinogenesis, however its significance in esophageal squamous cell carcinoma (ESCC) is uncertain. This research is intended to examine how RBM15 regulates the development of ESCC. We performed qRT-PCR analysis to evaluate the expression of RBM15, microRNA (miR-3605-5p) as well as keratin 4 (KRT4) in ESCC. Target relationship between miR-3605-5p and KRT4 was validated by dual luciferase reporter assay. Western blotting analyzed the protein levels of KRT4, p53, and p21. To demonstrate that RBM15 is responsible for the m6A alteration of miR-3605-5p, RIP and Me-RIP experiments were carried out concurrently. m6A content was measured by m6A quantification assay. Cell growth and migration were assessed using the CCK-8 and transwell assays. In addition, the role of RBM15 in vivo was examined using a mouse tumor xenograft model. RBM15 and miR-3605-5p were both substantially expressed in ESCC, however KRT4 was not expressed highly. Overexpressed RBM15 triggered cell proliferation and migration in ESCC. Besides, RBM15/m6A could mediate pri-3605-5p to form the mature miR-3605-5p, and miR-3605-5p further targeted KRT4. Further investigations showed that upregulation of KRT4 overturned the promoting impact of RBM15 overexpression on cell proliferation as well as on cell migration in ESCC by activating p53 signaling pathway. This work implied the carcinogenic activity of RBM15/m6A in ESCC via miR-3605-5p/KRT4 pathway, providing a novel m6A modification pattern in the tumorigenesis of ESCC.

2024-01-25·Experimental cell research

The m6A methyltransferase RBM15 affects tumor cell stemness and progression of cervical cancer by regulating the stability of lncRNA HEIH.

Article

作者: Yi Quan ; Muchuan Zhou ; Jinhong Li ; Yihong Yang ; Junliang Guo ; Tian Tang ; Ping Liu

Cervical cancer (CC), as a common female malignant tumor in the world, is an important risk factor endangering women's health worldwide. The purpose of this study was to investigate the role of RBM15 in CC. The TCGA database was used to screen differentially expressed m6A genes in normal and tumor tissues. QRT-PCR was used to quantify HEIH, miR-802, EGFR, cell stemness, and epithelial-mesenchymal transition (EMT)-related genes. The interaction between HEIH and miR-802 was verified by dual-luciferase reporter assay and RIP assay. The occurrence of tumor cells after different treatments was detected by CCK-8, transwell and EdU staining. BALB/c nude mice were used to examine the effects of different treatments on tumor growth and cell stemness in vivo. RBM15 was upregulated in tumor tissues and cells. M6A was highly enriched in HEIH and enhances its RNA stability. HEIH acts as an oncogenic lncRNA to promote CC cell proliferation, migration and tumor growth. Mechanistically, HEIH regulates tumor cell stemness and promotes the proliferation and migration of CC cells by competitively adsorbing miR-802 and up-regulating the expression of EGFR. In short, our data shown that the m6A methyltransferase RBM15 could affect tumor cell proliferation, metastasis and cell stemness by stabilizing HEIH expression.

项与 RBM15 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~

临床1期引进/卖出临床申请临床终止信使RNA

2023-09-01

·生物谷

填补缺失的关键环节：何川团队揭示染色质上m6A识别蛋白RBFOX2及其在白血病中的作用

这项研究表明了YTHDC1与PRC2复合物相互作用以抑制髓系细胞中染色质的可及性。当YTHDC1被募集到基因启动子区域时，不仅使m6A修饰的启动子相关RNA（paRNA）不稳定芝加哥大学何川教授、陈梦洁教授、希望之城医疗中心贝克曼研究所陈建军教授合作，在 Nature Cell Biology 期刊发表了题为：RBFOX2 recognizes N6-methyladenosine to suppress transcription and block myeloid leukaemia differentiation 的研究论文。该研究揭示了一个涉及甲基转移酶复合物（MTC）、“阅读器”YTHDC1和RNA结合蛋白RBFOX2的转录调控轴——RBFOX2将MTC组分RBM15招募到启动子相关RNA（paRNA）进行甲基化。RBM15进一步与YTHDC1相互作用，招募PRC2到RBFOX2结合位点进行转录抑制。RBFOX2-m6A-RBM15-YTHDC1-PRC2轴在髓系白血病中发挥重要作用，RBFOX2的下调显著抑制急性髓系白血病（AML）细胞的存活/增殖，并促进AML细胞的髓系分化。因此，RBFOX2被确定为一个染色质因子，在位点特异性染色质调控过程中促进m6A在染色质相关RNA（caRNA）上的积累。RBFOX2在急性髓系白血病（AML）中过表达，通过阻断髓系分化来维持白血病干细胞（LSCs）的生长和自我更新，为白血病的治疗提供了新的潜在靶点。该研究将一种已被充分研究的RNA结合蛋白RBFOX2鉴定为一种染色质因子，其优先识别染色质相关RNA（caRNA）上的m6A，RBFOX2可以募集甲基转移酶复合物（MTC）组分RBM15来促进启动子相关RNA（paRNA）的甲基化。RBM15还与YTHDC1相互作用，并招募PRC2到RBFOX2结合位点，从而进行染色质沉默和转录抑制。此外，该研究还发现了RBFOX2-m6A-RBM15-YTHDC1-PRC2轴在髓系白血病中发挥关键作用。RBFOX2的下调显著抑制急性髓系白血病（AML）细胞的生存/增殖并促进其髓系分化。RBFOX2也是白血病干细胞（LSCs）/起始细胞的自我更新和急性髓系白血病的维持所需要的。髓系白血病中RBFOX2与m6A修饰的caRNA的结合调控基因表达这项研究表明了YTHDC1与PRC2复合物相互作用以抑制髓系细胞中染色质的可及性。当YTHDC1被募集到基因启动子区域时，不仅使m6A修饰的启动子相关RNA（paRNA）不稳定，还介导H3K27三甲基化从而抑制转录，而这一过程依赖于RBFOX2。因此，该研究揭示了RBFOX2作为染色质上的m6A结合蛋白，发挥了促进染色质相关RNA（caRNA）甲基化从而抑制转录的功能。这种调控模式填补了染色质和caRNA的m6A甲基化之间相互作用的关键缺失环节。