更新于：2024-09-19

DDX39B

更新于：2024-09-19

基本信息

别名

56 kDa U2AF65-associated protein、ATP-dependent RNA helicase p47、BAT1

+ [7]

简介

Involved in nuclear export of spliced and unspliced mRNA. Assembling component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway. May undergo several rounds of ATP hydrolysis during assembly of TREX to drive subsequent loading of components such as ALYREF/THOC and CHTOP onto mRNA. Also associates with pre-mRNA independent of ALYREF/THOC4 and the THO complex. Involved in the nuclear export of intronless mRNA; the ATP-bound form is proposed to recruit export adapter ALYREF/THOC4 to intronless mRNA; its ATPase activity is cooperatively stimulated by RNA and ALYREF/THOC4 and ATP hydrolysis is thought to trigger the dissociation from RNA to allow the association of ALYREF/THOC4 and the NXF1-NXT1 heterodimer. Involved in transcription elongation and genome stability. (Microbial infection) The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. Splice factor that is required for the first ATP-dependent step in spliceosome assembly and for the interaction of U2 snRNP with the branchpoint. Has both RNA-stimulated ATP binding/hydrolysis activity and ATP-dependent RNA unwinding activity. Even with the stimulation of RNA, the ATPase activity is weak. Can only hydrolyze ATP but not other NTPs. The RNA stimulation of ATPase activity does not have a strong preference for the sequence and length of the RNA. However, ssRNA stimulates the ATPase activity much more strongly than dsRNA. Can unwind 5' or 3' overhangs or blunt end RNA duplexes in vitro. The ATPase and helicase activities are not influenced by U2AF2; the effect of ALYREF/THOC4 is reported conflictingly with [PubMed:23299939] reporting a stimulatory effect.

关联

100 项与 DDX39B 相关的临床结果

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100 项与 DDX39B 相关的转化医学

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0 项与 DDX39B 相关的专利（医药）

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176

项与 DDX39B 相关的文献（医药）

2024-11-01·Gene

Transcriptome analysis of human dental pulp cells cultured on a novel cell-adhesive fragment by RNA sequencing

Article

作者: Huang, Xiaofeng ; Tang, Jia

AIMThe aim of the present work was to find an efficient method for safe and reliable expansion of human dental pulp cells (hDPCs) in vitro. Here, we examined the effect of a novel recombinant E8 fragment of Laminin-511 (iMatrix-511) in hDPCs regarding viability and cell spreading. Further, we investigated the underlying mechanisms governing its effects in hDPCs using RNA sequencing (RNA-seq).METHODOLOGYhDPCs were obtained from caries-free maxilla third molars (n = 3). CCK-8 assay was conducted to measure the viability of cells cultured on iMatrix-511 and two other ECM proteins. Cell morphology was observed by phase contrast microscope. RNA-seq of hDPCs cultured on iMatrix-511 or noncoated control was performed on Illumina Novaseq^TM 6000 platform.RESULTSiMatrix-511 (0.5 μg/cm²) enhanced the viability of hDPCs to an extent better than COL-1 and gelatin. Short term culture of hDPCs on iMatrix-511 resulted in 233 differentially expressed genes (DEGs). The top 12 most upregulated genes were XIAP, AL354740, MRFAP1, AC012321, KCND3, TMEM120B, AC009812, GET1-SH3BGR, CNTN3, AC090409, GEN1 and PIK3IP1, whereas the top 12 most downregulated genes were SFN, KRT17, RAB4B-EGLN2, CSTA, KCTD11, ATP6V1G2-DDX39B, AC010323, SBSN, LYPD3, FOSB, AC022400 and CHI3L1. qPCR validation confirmed the significant upregulation of GEN1, KCND3, PIK3IP1 and MRFAP1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, with genes enriched in various extracellular matrix interaction, estrogen and fat metabolism-related functions and pathways.CONCLUSIONSiMatrix-511 facilitated spreading and proliferation of hDPCs. It enhances expression of anti-apoptotic genes, while inhibits expression of epidermis development-related genes.

2024-08-12·Nucleic Acids Research

Parsing the roles of DExD-box proteins DDX39A and DDX39B in alternative RNA splicing

Article

作者: Garcia-Blanco, Mariano A ; Nagasawa, Chloe K ; Banerjee, Shefali ; Widen, Steven G

AbstractDExD-box RNA proteins DDX39A and DDX39B are highly homologous paralogs that are conserved in vertebrates. They are required for energy-driven reactions involved in RNA processing. Although we have some understanding of how their functions overlap in RNA nuclear export, our knowledge of whether or not these proteins have specific or redundant functions in RNA splicing is limited. Our previous work has shown that DDX39B is responsible for regulating the splicing of important immune transcripts IL7R and FOXP3. In this study, we aimed to investigate whether DDX39A, a highly homologous paralog of DDX39B, plays a similar role in regulating alternative RNA splicing. We find that DDX39A and DDX39B have significant redundancy in their gene targets, but there are targets that uniquely require one or the other paralog. For instance, DDX39A is incapable of complementing defective splicing of IL7R exon 6 when DDX39B is depleted. This exon and other cassette exons that specifically depend on DDX39B have U-poor/C-rich polypyrimidine tracts in the upstream intron and this variant polypyrimidine tract is required for DDX39B dependency. This study provides evidence that despite a high degree of functional redundancy, DDX39A and DDX39B are selectively required for the splicing of specific pre-mRNAs.

2024-08-01·International Immunopharmacology

CircZNF609 inhibited bladder cancer immunotherapy sensitivity via enhancing fatty acid uptake through IGF2BP2/CD36 pathway

Article

作者: Wang, Jun ; Zhu, Qingyi ; Li, Kai ; Wei, Yong ; Zhang, Yetao ; Lv, Jiancheng ; Lin, Jianzhong

Circular RNAs (circRNAs) are gaining attention for their involvement in immune escape and immunotherapy sensitivity regulation. CircZNF609 is a well-known oncogene in various solid tumours. Our previous research revealed its role in reducing the chemosensitivity of bladder cancer (BCa) to cisplatin. However, the underlying role of circZNF609 in BCa immune escape and immunotherapy sensitivity remains unknown. We conducted BCa cells-CD8 + T cells co-culture assays, cell line-derived xenograft and patient-derived xenograft mouse models with human immune reconstitution to further confirm the role of circZNF609 in BCa immune escape and immunotherapy sensitivity. Overexpression of circZNF609 promoted BCa immune escape in vitro and in vivo. Mechanistically, circZNF609 was bound to IGF2BP2, enhancing its interaction with the 3'-untranslated region of CD36. This increased the stability of the CD36 mRNA, leading to enhanced fatty acid uptake by BCa cells and fatty acid depletion within the tumour microenvironment. Additionally, the nuclear export of circZNF609 was regulated by DDX39B. CircZNF609 promoted immune escape and suppressed BCa immunotherapy sensitivity by regulating the newly identified circZNF609/IGF2BP2/CD36 cascade. Therefore, circZNF609 holds potential as both a biomarker and therapeutic target in BCa immunotherapy.

项与 DDX39B 相关的新闻（医药）

2022-08-20

·生物制品圈

华西医院科学家发现肿瘤代谢治疗新靶点！

导读：肿瘤细胞即使在氧气充足的情况下也会通过糖酵解方式来进行代谢，消耗大量葡萄糖并最终生成乳酸，这种现象被称为肿瘤的有氧糖酵解，也叫做Warburg效应。在这一过程中存在一个重要的调节因子，即M2型丙酮酸激酶 (PKM2)，该酶催化其上游底物磷酸烯醇式丙酮酸PEP生成丙酮酸。PKM2在增殖的细胞尤其是肿瘤细胞中高表达。8月17日，四川大学华西医院林苹教授及李凯教授《Signal Transduction and Targeted Therapy》合作发表了一项研究“DDX39B drives colorectal cancer progression by promoting the stability and nuclear translocation of PKM2”，发现DDX39B 通过促进 PKM2 介导的代谢重编程驱动结直肠癌的进展。Doi: 10.1038/s41392-022-01096-7.研究背景 01 结直肠癌 (CRC) 是发病率排名第三的恶性肿瘤，最近的研究表明，代谢重编程对于肿瘤发生和转移至关重要。PKM2作为糖酵解途径关键的限速酶，在多种肿瘤中显著上调。最近发现PKM2 还可以转移到细胞核中，在细胞核中发挥蛋白激酶和共转录因子的作用，导致代谢和增殖基因的反式激活，然而，PKM2 在肿瘤发生过程中动态积累和核定位的分子机制仍不完全清楚。人类 DExD-box 解旋酶 39B (DDX39B) 是 DEAD-box 蛋白家族的成员，参与 RNA 代谢的许多步骤，在肿瘤中发生发展中起到至关重要的作用，然而，DDX39B在CRC中的具体作用和详细机制尚不清楚。研究过程 02 研究人员通过GEO数据库鉴定出与CRC发生和转移相关的靶基因DDX39B（图1），并通过TCGA数据库及大样本临床数据进行验证，发现DDX39B在CRC中显著高表达且与CRC患者预后负相关，且在体内及体外促进CRC的生长和转移。研究人员为进一步确定 DDX39B 在 CRC 中上调的机制，通过分析DDX39B 的启动子并进行验证，发现Sp1可激活 CRC 细胞中的 DDX39B 转录。图1. 通过GEO数据库筛选与CRC发生和转移相关的靶基因此外，研究人员为明确DDX39B发挥作用的机制，通过免疫沉淀联合质谱技术鉴定出DDX39B的相互作用蛋白PKM2，并发现DDX39B 与 PKM2 的相互作用可防止其降解，且DDX39B可促进不依赖 ERK 的 PKM2 核转位（图2），而DDX39B 可以通过增强 CRC 细胞的核 PKM2 功能促进有氧糖酵解进而促进肿瘤进展。图2. DDX39B促进不依赖 ERK 的 PKM2 核转位为进一步明确DDX39B与PKM2的互作机制，研究人员通过结构生物信息学分析了DDX39B与PKM2的空间结构并进行对接测试，发现DDX39B 上的 Arg319 是 PKM2 结合和 DDX39B 促进 CRC 发生和发展的能力所必需的（图3）。此外，研究人员亦发现核 PKM2 介导的 Warburg 效应对于 DDX39B 触发的 CRC 致瘤性和转移也是必不可少的。图3. Arg319 对于DDX39B 促进 CRC发生和发展至关重要研究意义 05 这项研究将 DDX39B 确定为导致 CRC 恶性进展的 Warburg 效应的关键启动子，揭示了 DDX39B 的临床价值，并为 DDX39B介导的代谢可塑性提供了理论依据，通过筛选靶向 DDX39B 或阻断 DDX39B-PKM2 结合的抑制剂可能是 CRC治疗的新策略。参考资料：Zhao G, Yuan H, Li Q, et.al. DDX39B drives colorectal cancer progression by promoting the stability and nuclear translocation of PKM2. Signal Transduct Target Ther. 2022 Aug 17;7(1):275. doi: 10.1038/s41392-022-01096-7.

2022-08-16

·生物谷

The Plant Cell:揭示可变剪接调控光形态建成的分子机制

太阳光是植物光合作用的能量来源，也是重要的环境信号，调节植物的生长发育进程。其中，幼苗光形态建成受光质、光量的精确调控，涉及不同的光受体和一系列信号调控因子。COP1是光形态建成的一个明星蛋白，作为太阳光是植物光合作用的能量来源，也是重要的环境信号，调节植物的生长发育进程。其中，幼苗光形态建成受光质、光量的精确调控，涉及不同的光受体和一系列信号调控因子。COP1是光形态建成的一个明星蛋白，作为一种E3泛素连接酶，与目标蛋白互作并促进其降解，COP1在植物和动物中广泛存在。真核生物的基因多含有内含子，转录形成前体mRNA，通过动态剪接组装，形成成熟的mRNA。可变剪接又称选择性剪接，是重要的基因转录后调控机制，在特定位点发生剪接从而生成多种mRNA，翻译成不同蛋白质，在相应的发育时期发挥重要功能。近年来，有研究通过转录组分析了光照对于可变剪接的调控现象，而具体调控机制尚不清楚。中国科学院植物研究所研究员林荣呈研究组鉴定到RNA解旋酶UAP56是调控光形态建成的一个新因子。UAP56在拟南芥中有两个高度同源的成员UAP56a和UAP56b，位于染色体上相邻的位置。研究从遗传学入手，发现UAP56a和UAP56b功能冗余，但两者纯合致死，利用uap56a纯合与uap56b杂合的突变材料，证明UAP56参与光敏色素和隐花色素光受体介导的光形态建成信号通路中，是一个负向调控因子。研究通过寻找互作蛋白，发现UAP56、COP1以及剪接辅助因子U2AF65直接相互作用。研究进一步利用Nanopore三代转录组测序技术，发现在黑暗及光照条件下，UAP56和COP1调控了大量基因的转录与可变剪接，包括较多植物生长发育、光合作用以及光信号因子等相关基因均受二者转录或剪接的调控。进一步的RNA免疫沉淀实验显示，UAP56和COP1可以直接结合到剪接体和靶基因的mRNA上，表明UAP56和COP1可以通过作用于剪接体从而直接调控光信号介导的选择性剪接。该研究鉴定到光形态建成的新成员UAP56，发现了COP1作为可变剪接调节因子的新功能，揭示了UAP56与COP1共同通过调节下游基因可变剪接来调控光形态建成的分子机制和调控网络，增加了对于植物光信号转导机制的认识。同时，UAP56在植物、酵母、动物等均广泛存在，具有保守的RNA解旋酶结构，UAP56-COP1的作用方式为探究其他物种的类似机制提供了重要参考。相关研究成果在线发表在The Plant Cell上。研究工作得到国家重点研发计划、国家自然科学基金、中科院的支持。