更新于：2024-09-05

YBX3

更新于：2024-09-05

基本信息

别名

Cold shock domain-containing protein A、CSDA、CSDA1

+ [7]

简介

Binds to the GM-CSF promoter. Seems to act as a repressor. Binds also to full-length mRNA and to short RNA sequences containing the consensus site 5'-UCCAUCA-3'. May have a role in translation repression (By similarity).

关联

100 项与 YBX3 相关的临床结果

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100 项与 YBX3 相关的转化医学

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0 项与 YBX3 相关的专利（医药）

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413

项与 YBX3 相关的文献（医药）

2024-03-01·Molecular breeding : new strategies in plant improvement

PbrCSP1, a pollen tube-specific cold shock domain protein, is essential for the growth and cold resistance of pear pollen tubes.

Article

作者: Xiaoxuan Zhu ; Chao Tang ; Ting Zhang ; Shaoling Zhang ; Juyou Wu ; Peng Wang

Cold shock domain proteins (CSPs), initially identified in Escherichia coli, have been demonstrated to play a positive role in cold resistance. Previous studies in wheat, rice, and Arabidopsis have indicated the functional conservation of CSPs in cold resistance between bacteria and higher plants. However, the biological functions of PbrCSPs in pear pollen tubes, which represent the fragile reproductive organs highly sensitive to low temperature, remain largely unknown. In this study, a total of 22 CSPs were identified in the seven Rosaceae species, with a focus on characterizing four PbrCSPs in pear (Pyrus bretschneideri Rehder). All four PbrCSPs were structurally conserved and responsive to the abiotic stresses, such as cold, high osmotic, and abscisic acid (ABA) treatments. PbrCSP1, which is specifically expressed in pear pollen tubes, was selected for further research. PbrCSP1 was localized in both the cytoplasm and nucleus. Suppressing the expression of PbrCSP1 significantly inhibited the pollen tube growth in vitro. Conversely, overexpression of PbrCSP1 promoted the growth of pear pollen tubes under the normal condition and, notably, under the cold environment at 4 °C. These findings highlight an essential role of PbrCSP1 in facilitating the normal growth and enhancing cold resistance in pear pollen tubes.

Supplementary Information:

The online version contains supplementary material available at 10.1007/s11032-024-01457-w.

2024-01-19·Pediatric rheumatology online journal

Establishment and analysis of a novel diagnostic model for systemic juvenile idiopathic arthritis based on machine learning.

Article

作者: Pan Ding ; Yi Du ; Xinyue Jiang ; Huajian Chen ; Li Huang

BACKGROUND:

Systemic juvenile idiopathic arthritis (SJIA) is a form of childhood arthritis with clinical features such as fever, lymphadenopathy, arthritis, rash, and serositis. It seriously affects the growth and development of children and has a high rate of disability and mortality. SJIA may result from genetic, infectious, or autoimmune factors since the precise source of the disease is unknown. Our study aims to develop a genetic-based diagnostic model to explore the identification of SJIA at the genetic level.

METHODS:

The gene expression dataset of peripheral blood mononuclear cell (PBMC) samples from SJIA was collected from the Gene Expression Omnibus (GEO) database. Then, three GEO datasets (GSE11907-GPL96, GSE8650-GPL96 and GSE13501) were merged and used as a training dataset, which included 125 SJIA samples and 92 health samples. GSE7753 was used as a validation dataset. The limma method was used to screen differentially expressed genes (DEGs). Feature selection was performed using Lasso, random forest (RF)-recursive feature elimination (RFE) and RF classifier.

RESULTS:

We finally identified 4 key genes (ALDH1A1, CEACAM1, YBX3 and SLC6A8) that were essential to distinguish SJIA from healthy samples. And we combined the 4 key genes and performed a grid search as well as 10-fold cross-validation with 5 repetitions to finally identify the RF model with optimal mtry. The mean area under the curve (AUC) value for 5-fold cross-validation was greater than 0.95. The model's performance was then assessed once more using the validation dataset, and an AUC value of 0.990 was obtained. All of the above AUC values demonstrated the strong robustness of the SJIA diagnostic model.

CONCLUSIONS:

We successfully developed a new SJIA diagnostic model that can be used for a novel aid in the identification of SJIA. In addition, the identification of 4 key genes that may serve as potential biomarkers for SJIA provides new insights to further understand the mechanisms of SJIA.

2024-01-06·bioRxiv : the preprint server for biology

Behavioral screening of conserved RNA-binding proteins reveals CEY-1/YBX RNA-binding protein dysfunction leads to impairments in memory and cognition.

作者: Ashley N Hayden ; Katie L Brandel ; Paul R Merlau ; Priyadharshini Vijayakumar ; Emily J Leptich ; Edward W Pietryk ; Elizabeth S Gaytan ; Connie W Ni ; Hsiao-Tuan Chao ; Jill A Rosenfeld ; Rachel N Arey

RNA-binding proteins (RBPs) are key regulators of translation and plasticity in the nervous system, which are processes required for learning and memory. Indeed, RBP dysfunction has been linked to a wide range of neurological disorders where cognitive impairments are a key symptom. However, the human genome encodes nearly 2,000 RBPs, many of which have yet to be characterized with regards to neurological phenotypes like associative behaviors. To address this, we used the model organism C. elegans to perform a targeted screen assessing the role of 20 conserved RBPs in learning and memory. We identified 16 associative memory regulators, eight of which are novel. Intriguingly, three novel memory regulators are in the C. elegans Y-Box (CEY) RNA-binding protein family: cey-1, cey-2 , and cey-3 . We determined that cey-1 is the closest ortholog to the mammalian Y-Box RNA-binding (YBX) proteins and that CEY-1 is specifically required in the nervous system for the ability to remember. Additionally, CEY-1 is a memory promoting molecule, as increasing CEY-1 only in the nervous system improves memory. We also examined human copy number variation datasets and found that copy number deletions in the human YBX1 and YBX3 may be associated with neurological symptoms including intellectual disability, which mirror our findings in C. elegans . We identified a similar association with a rare, mono-allelic YBX3 variant in individuals with neurological findings. Strikingly, introducing this predicted deleterious YBX3 variant into the endogenous cey-1 locus caused memory deficits in the worm. Our study highlights that high-throughput approaches in the worm reveal novel and conserved regulators of memory and identified a potential new source of rare neurological disease linked to RBP dysfunction.

项与 YBX3 相关的新闻（医药）

2023-09-18

·生物谷

《自然·癌症》：华西医院团队破解癌症早期发展之谜，有望催生防癌新疗法

综上，该研究创建了两种新型mutp53荧光融合蛋白报告基因鼠，能可视化mutp53的分子功能，可在病理正常的组织中对早期癌前细胞进行特异性标记、追踪和靶向干预，为研究肿瘤早期演进过程铺平了道路。近期，四川大学华西生物治疗国家重点实验室汪源团队利用基因编辑技术，构建了两种突变P53（mutp53）荧光融合蛋白报告基因鼠，可模拟mutp53蛋白在体内的功能和动态，不仅能在包括脑瘤、肉瘤、淋巴瘤等多种恶性肿瘤形成前，组织病理学无明显异常的情况下，特异性地识别、标记出那些mutp53蛋白高积累的癌前细胞，还能追踪肿瘤发生发展全过程。此外，研究团队还在胸腺淋巴瘤模型中发现，mutp53蛋白高积累的癌前细胞存在独特的基因组特征，如调控氨基酸转运代谢的基因Ybx3表达上调。若在早期肿瘤发生过程中使用氨基酸转运抑制剂JPH203治疗，可有效抑制肿瘤发生并延长小鼠生存时间。研究成果发表在《自然·癌症》上，姚朋乐、肖鹏和黄宗瑶是论文的共同第一作者。论文首页截图 P53可以说是人类癌症中最常见的基因突变，一半以上的癌症中都存在mutp53。汪源团队既往研究发现，在恶性脑胶质瘤模型中，mutp53蛋白不仅会在终末期肿瘤中高度积累，也会在病理正常的脑组织的癌前细胞中高度积累，具有特异性地标记癌前细胞的潜力。于是，汪源团队就想利用mutp53蛋白的高度积累，来观察和量化肿瘤早期演变过程。不过传统的mutp53检测，主要还是靠免疫组化，如何在病理正常的组织中观察、追踪并分离那些mutp53蛋白高度累积且最终会发展成肿瘤的癌前细胞，是个难题。更难的是，当时根本没有研究肿瘤发生与演进的肿瘤基因工程小鼠模型。那怎么办？自己造呗。经过不断的尝试，汪源团队最终利用基因编辑技术构建了两种mutp53融合蛋白报告基因鼠，p53-mCherry-KI（PC）和p53R172H-Akaluc（PAL），前者可以观察肿瘤和癌前细胞中的mutp53蛋白积累程度，并对癌前细胞进行流式分选，后者能通过新型荧光素酶系统，标记深层组织中的微量细胞。两种mutp53融合蛋白报告基因鼠在本研究中，汪源团队先是通过体外实验证明了PAL和PC均能很好地模拟热门mutp53（如p53R172H）的分子动力学和功能。随后，通过小鼠杂交获得的包括脑瘤、肉瘤、淋巴瘤等多种恶性实体瘤小鼠模型，也证明了PAL和PC中的mutp53单独或联合其他致癌基因可以驱动多种类型肿瘤的发生。此外，汪源团队还在多种肿瘤细胞中观察到PAL和PC融合蛋白的特异性积累，能通过PAL和PC可视化追踪脑瘤、肉瘤及恶性淋巴瘤等肿瘤的发生发展过程。接下来，为了探究PAL和PC能否追踪到正常组织中的癌前细胞，汪源团队决定用PCL小鼠（即通过PAL和PC杂交构建的Trp53PAL/PC小鼠模型，会发展为胸腺淋巴瘤）进行一次示范性研究。在构建的13只PCL小鼠中有9只在不同年龄段进展为胸腺淋巴瘤。起初，汪源团队只能在这些小鼠胸腺区域发现一些基础水平的、分布均匀的发光信号（RSI），随着小鼠年龄增长，这些信号开始变强，最大强度是基础水平的5-6倍。为了更好地量化发光强度，研究人员将高于基础水平2-3倍的RSI定义为发光灶，在发光灶出现后的4-6周里，所有小鼠均会进展为胸腺淋巴瘤。 13只PCL小鼠的RSI变化情况进一步，汪源团队想知道发光灶能否代表癌前病变，于是就对6只首次检测到发光灶的小鼠进行了组织学分析。结果发现，出现发光灶时，尽管小鼠胸腺大小和形态与同龄对照小鼠没有区别，但实际上已经出现了一些mutp53阳性异常细胞（细胞核形态改变）。这些异常细胞会在接下来的4-6周里高度积累，最终发展成小肿瘤（RSI=3.8）。也就是说，发光灶可以作为癌前病变的信号。组织学分析结果利用这些发光灶，研究人员可以在肿瘤发生前1-2月内，对癌前细胞进行标记。接下来的流式分选和T细胞受体测序结果也显示，即使在癌前细胞比例较低的情况下，PAL和PC依然可以将其进行特异性标记。现在工具问题解决了，那么接下来汪源团队需要解决的是，在癌症发生前，能否通过预防性治疗抑制肿瘤发生呢？为了解决这一问题，汪源团队对流式分选获得的mutp53高积累癌前细胞进行单细胞转录组分析。结果发现，这些癌前细胞具有广泛的染色体拷贝数变异以及独特的不同于正常细胞的转录组特征，如调控氨基酸转运、代谢的相关基因Ybx3表达上调。进一步，汪源团队发现，Ybx3可以通过控制其下游氨基酸转运蛋白Lat1/CD98来调控氨基酸的代谢。于是研究人员以Ybx3-Lat1/CD98为干预靶标，利用已经进入1期临床试验的Lat1/CD98抑制剂JPH203对PCL小鼠进行预防性治疗。具体来说，一旦出现发光灶，就开始治疗。结果显示，所有接受JPH203治疗的小鼠，发光信号以肉眼可见的速度变弱，2天内就能降到1RSI以下。此外，相较同龄对照小鼠，JPH203治疗组的中位生存期增加了71%。更重要的是，一半以上的小鼠都未进展为胸腺淋巴瘤。不过需要注意的是，JPH203只在早期，即出现发光灶时进行干预治疗才有效，当RSI>6时，接受JPH203治疗的小鼠没有任何生存获益。早期肿瘤发生过程中使用JPH203治疗，可有效抑制肿瘤发生并延长小鼠生存时间综上，该研究创建了两种新型mutp53荧光融合蛋白报告基因鼠，能可视化mutp53的分子功能，可在病理正常的组织中对早期癌前细胞进行特异性标记、追踪和靶向干预，为研究肿瘤早期演进过程铺平了道路。