更新于：2024-09-19

CNBP

更新于：2024-09-19

基本信息

别名

CCHC-type zinc finger nucleic acid binding protein、Cellular nucleic acid-binding protein、CNBP

+ [6]

简介

Single-stranded DNA-binding protein that preferentially binds to the sterol regulatory element (SRE) sequence 5'-GTGCGGTG-3', and thereby mediates transcriptional repression (PubMed:2562787). Has a role as transactivator of the Myc promoter (By similarity). Binds single-stranded RNA in a sequence-specific manner (By similarity). Binds G-rich elements in target mRNA coding sequences (PubMed:28329689). Prevents G-quadruplex structure formation in vitro, suggesting a role in supporting translation by resolving stable structures on mRNAs (PubMed:28329689). Binds to RNA. Binds to RNA. Binds to RNA. Binds to RNA. Binds to RNA.

关联

100 项与 CNBP 相关的临床结果

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100 项与 CNBP 相关的转化医学

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0 项与 CNBP 相关的专利（医药）

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309

项与 CNBP 相关的文献（医药）

2024-08-01·Plant Biotechnology Journal

miR396b/GRF6 module contributes to salt tolerance in rice

Article

作者: Li, Shaoqing ; Wang, Ruihua ; Si, Fengfeng ; Wang, Zhikai ; Cheng, Mingxing ; Wang, Wei ; Gao, Feng ; Yuan, Huanran ; Fan, Fengfeng

SummarySalinity, as one of the most challenging environmental factors restraining crop growth and yield, poses a severe threat to global food security. To address the rising food demand, it is urgent to develop crop varieties with enhanced yield and greater salt tolerance by delving into genes associated with salt tolerance and high‐yield traits. MiR396b/GRF6 module has previously been demonstrated to increase rice yield by shaping the inflorescence architecture. In this study, we revealed that miR396b/GRF6 module can significantly improve salt tolerance of rice. In comparison with the wild type, the survival rate of MIM396 and OE‐GRF6 transgenic lines increased by 48.0% and 74.4%, respectively. Concurrent with the increased salt tolerance, the transgenic plants exhibited reduced H2O2 accumulation and elevated activities of ROS‐scavenging enzymes (CAT, SOD and POD). Furthermore, we identified ZNF9, a negative regulator of rice salt tolerance, as directly binding to the promoter of miR396b to modulate the expression of miR396b/GRF6. Combined transcriptome and ChIP‐seq analysis showed that MYB3R serves as the downstream target of miR396b/GRF6 in response to salt tolerance, and overexpression of MYB3R significantly enhanced salt tolerance. In conclusion, this study elucidated the potential mechanism underlying the response of the miR396b/GRF6 network to salt stress in rice. These findings offer a valuable genetic resource for the molecular breeding of high‐yield rice varieties endowed with stronger salt tolerance.

2024-06-01·Acta Neuropathologica

Multi-level profiling unravels mitochondrial dysfunction in myotonic dystrophy type 2

Article

作者: Kleefeld, Felix ; Schoser, Benedikt ; Sickmann, Albert ; Hathazi, Denisa ; Pinal-Fernandez, Iago ; Hentschel, Andreas ; Melchert, Sarah ; Horvath, Rita ; Mammen, Andrew L ; Preuße, Corinna ; Casal-Dominguez, Maria ; Stenzel, Werner ; Hahn, Katrin ; Muselmann-Genschow, Claudia ; Roos, Andreas

AbstractMyotonic dystrophy type 2 (DM2) is an autosomal-dominant multisystemic disease with a core manifestation of proximal muscle weakness, muscle atrophy, myotonia, and myalgia. The disease-causing CCTG tetranucleotide expansion within the CNBP gene on chromosome 3 leads to an RNA-dominated spliceopathy, which is currently untreatable. Research exploring the pathophysiological mechanisms in myotonic dystrophy type 1 has resulted in new insights into disease mechanisms and identified mitochondrial dysfunction as a promising therapeutic target. It remains unclear whether similar mechanisms underlie DM2 and, if so, whether these might also serve as potential therapeutic targets. In this cross-sectional study, we studied DM2 skeletal muscle biopsy specimens on proteomic, molecular, and morphological, including ultrastructural levels in two separate patient cohorts consisting of 8 (explorative cohort) and 40 (confirmatory cohort) patients. Seven muscle biopsy specimens from four female and three male DM2 patients underwent proteomic analysis and respiratory chain enzymology. We performed bulk RNA sequencing, immunoblotting of respiratory chain complexes, mitochondrial DNA copy number determination, and long-range PCR (LR-PCR) to study mitochondrial DNA deletions on six biopsies. Proteomic and transcriptomic analyses revealed a downregulation of essential mitochondrial proteins and their respective RNA transcripts, namely of subunits of respiratory chain complexes I, III, and IV (e.g., mt-CO1, mt-ND1, mt-CYB, NDUFB6) and associated translation factors (TACO1). Light microscopy showed mitochondrial abnormalities (e.g., an age-inappropriate amount of COX-deficient fibers, subsarcolemmal accumulation) in most biopsy specimens. Electron microscopy revealed widespread ultrastructural mitochondrial abnormalities, including dysmorphic mitochondria with paracrystalline inclusions. Immunofluorescence studies with co-localization of autophagy (p62, LC-3) and mitochondrial marker proteins (TOM20, COX-IV), as well as immunohistochemistry for mitophagy marker BNIP3 indicated impaired mitophagic flux. Immunoblotting and LR-PCR did not reveal significant differences between patients and controls. In contrast, mtDNA copy number measurement showed a reduction of mtDNA copy numbers in the patient group compared to controls. This first multi-level study of DM2 unravels thus far undescribed functional and structural mitochondrial abnormalities. However, the molecular link between the tetranucleotide expansion and mitochondrial dysfunction needs to be further elucidated.

2024-04-01·Journal of Molecular and Cellular Cardiology

Cellular nucleic acid binding protein facilitates cardiac repair after myocardial infarction by activating β-catenin signaling

Article

作者: Guo, Xuejiang ; Du, Chong ; Zhao, Shan ; Wang, Hao ; Jiang, Qiqi ; Wang, Sibo ; Wei, Tianwen ; Chen, Jiawen ; Wang, Liansheng ; Yang, Tongtong ; Gu, Lingfeng ; Shan, Tiankai ; Han, Xudong

The regenerative capacity of the adult mammalian heart is limited, while the neonatal heart is an organ with regenerative and proliferative ability. Activating adult cardiomyocytes (CMs) to re-enter the cell cycle is an effective therapeutic method for ischemic heart disease such as myocardial infarction (MI) and heart failure. Here, we aimed to reveal the role and potential mechanisms of cellular nucleic acid binding protein (CNBP) in cardiac regeneration and repair after heart injury. CNBP is highly expressed within 7 days post-birth while decreases significantly with the loss of regenerative ability. In vitro, overexpression of CNBP promoted CM proliferation and survival, whereas knockdown of CNBP inhibited these processes. In vivo, knockdown of CNBP in CMs robustly hindered myocardial regeneration after apical resection in neonatal mice. In adult MI mice, CM-specific CNBP overexpression in the infarct border zone ameliorated myocardial injury in acute stage and facilitated CM proliferation and functional recovery in the long term. Quantitative proteomic analysis with TMT labeling showed that CNBP overexpression promoted the DNA replication, cell cycle progression, and cell division. Mechanically, CNBP overexpression increased the expression of β-catenin and its downstream target genes CCND1 and c-myc; Furthermore, Luciferase reporter and Chromatin immunoprecipitation (ChIP) assays showed that CNBP could directly bind to the β-catenin promoter and promote its transcription. CNBP also upregulated the expression of G1/S-related cell cycle genes CCNE1, CDK2, and CDK4. Collectively, our study reveals the positive role of CNBP in promoting cardiac repair after injury, providing a new therapeutic option for the treatment of MI.

项与 CNBP 相关的新闻（医药）

2023-12-24

·生物探索

EHJ | 复旦大学葛均波/翁鑫宇发现心肌梗死驱动单核细胞的训练免疫，加速动脉粥样硬化

尽管先进的医学治疗，急性冠状动脉综合征的幸存者仍面临着动脉粥样硬化相关血管事件复发的高风险，其根本原因尚不清楚。2023年12月12日，复旦大学葛均波及翁鑫宇共同通讯（第一作者董正）在European Heart Journal（IF=39）在线发表题为“Myocardial infarction drives trained immunity of monocytes, accelerating atherosclerosis”的研究论文，该研究证明心肌梗死驱动单核细胞的训练免疫（trained immunity），加速动脉粥样硬化。在MI和IR小鼠中，暴露于HFD或氧化低密度脂蛋白(oxLDL)刺激后，血液单核细胞和骨髓源性巨噬细胞表现出脾脏酪氨酸激酶(SYK)、赖氨酸甲基转移酶5A (KMT5A)和CCHC型锌指核酸结合蛋白(CNBP)表达升高。MI诱导的训练免疫可通过骨髓移植传播，加速初代受者的动脉粥样硬化。KMT5A特异性地将组蛋白H4的Lys20单甲基化(H4K20me)募集到SYK的基因体上，并与CNBP协同反激活SYK。体内小干扰RNA (siRNA)抑制KMT5A或CNBP可能减缓心肌梗死后动脉粥样硬化。6-羟多巴胺去交感神经能减少心肌梗死后动脉粥样硬化和炎症。ST段抬高型心肌梗死(STEMI)晚期冠状动脉病变患者的经典单核细胞表达更高的SYK和KMT5A基因水平。这些发现强调了单核细胞训练免疫在心肌梗死后加速动脉粥样硬化中的关键作用，这意味着血液经典单核细胞中的SYK可能是STEMI患者动脉粥样硬化进展的预测因素。尽管由于心血管医学技术的进步，越来越多的急性心肌梗死(MI)患者得到了及时有效的治疗，但心肌梗死后动脉粥样硬化相关血管事件复发的高风险仍持续多年。先前的研究已经证实，在心肌梗死、下肢缺血或中风等缺血事件后，动脉狭窄伴动脉粥样硬化作为潜在病理过程的发生率显著增加。动脉粥样硬化是一种以脂质和免疫细胞在血管内膜逐渐积聚，导致动脉粥样硬化形成为特征的病理过程在这个过程中，单核细胞和巨噬细胞在浸润到动脉病变后起着至关重要的作用。目前的临床研究也表明，调节单核细胞的表型可以减轻动脉粥样硬化及其临床并发症在小鼠中，心肌梗死通过刺激骨髓(BM)肾上腺素能受体加速动脉粥样硬化的进展，从而驱动单核细胞进入循环，进而促进动脉粥样硬化的发生。虽然单核细胞的循环寿命约为一周，但心肌梗死后动脉粥样硬化复发的风险可持续数年甚至数十年，其中的机制尚不完全清楚。最近，有研究表明，先天免疫细胞保留了先前暴露于微生物或炎症损伤的记忆，使它们能够对未来遇到相同或不相关的刺激产生更强的反应。这种被称为“训练免疫”的现象受到表观遗传机制和代谢重编程的强烈调节，这可能导致先天免疫细胞持久的促炎表型。在病理条件下，慢性炎症性疾病可以通过训练免疫增加对另一种炎症引发疾病的易感性。例如，来自牙周炎患者或实验性牙周炎模型小鼠的单核细胞受到适应性不良的脑卒中介导的免疫过程的训练，从而促进骨关节炎的发生。机理模式图（图源自European Heart Journal ）经过训练的免疫力也会促进动脉粥样硬化的发生和发展先前的研究表明，抗炎疗法可以降低复发性心血管事件。该发现缺血后小鼠经历了明显的免疫训练，激活全身炎症，并通过赖氨酸甲基转移酶5A (KMT5A)和cchc型锌指核酸结合蛋白(CNBP)在单核细胞中增加SYK(脾酪氨酸激酶)的表达。这些发现在从人外周血中提取的经典单核细胞中得到进一步验证。该研究证实单核细胞的免疫训练加速心肌梗死后动脉粥样硬化，单核细胞中的SYK可能是预防心肌梗死后动脉粥样硬化进展的分子靶点。参考文献：Dong Z, Hou L, Luo W, Pan LH,et al. Myocardial infarction drives trained immunity of monocytes, accelerating atherosclerosis. Eur Heart J. 2023 Dec 12:ehad787. doi: 10.1093/eurheartj/ehad787. Epub ahead of print. PMID: 38085922.文章来源：“iNature”责编|探索君排版|探索君End往期精选围观王晓红教授团队：绘制单次冷冻囊胚移植成功的女性植入期外周血microRNA动态表达谱，开拓领域创新研究热文维生素B12在细胞重编程与组织再生中发挥关键作用！热文不孕症治疗新方向！又一导致女性不孕的关键因素被发现热文Let-7家族miRNA或为癌症潜在免疫治疗靶点热文一项最新发现或可用于阿尔茨海默病药物开发点击“阅读原文”，了解更多~

siRNA临床研究