OAS3

更新于：2025-05-07

基本信息

别名

(2-5')oligo(A) synthase 3、2-5A synthase 3、2'-5'-oligoadenylate synthase 3

+ [4]

简介

Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes preferentially dimers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. Displays antiviral activity against Chikungunya virus (CHIKV), Dengue virus, Sindbis virus (SINV) and Semliki forest virus (SFV).

关联

100 项与 OAS3 相关的临床结果

登录后查看更多信息

100 项与 OAS3 相关的转化医学

登录后查看更多信息

0 项与 OAS3 相关的专利（医药）

登录后查看更多信息

226

项与 OAS3 相关的文献（医药）

2025-04-01·Genes & Genomics

BRN3A, a transcription factor, regulates the expression of genes involved in biological processes shaping the HPV induced cervical cancer

Article

作者: Roy, Jagat Kumar ; Prakash, Anand ; Patel, Yashvant

BACKGROUNDCervical cancer is the fourth most common cancer worldwide in females. This occurs primarily due to the infection of high-risk Human Papilloma Virus (HPV), although in advanced stages it requires support from host cellular factors. BRN3A is one such host cellular factors, whose expression remains high in cervical cancers and upregulates tumorigenic HPV gene expression. The effect of BRN3A on HPV-mediated cervical cancer and the underlying mechanism remains obscure.OBJECTIVETo investigates the effect of BRN3A on cancer-promoting biological processes in HPV-positive uterine cervix cancer cells.METHODSWe have altered the expression of BRN3A through over-expression (OE) and knock-down (KD) constructs in cervical cancer cell line, SiHa, and did transcriptome profiling through next-generation RNA-sequencing, validation through RT-PCR and BRN3A binding study with in silico promoter study and ChIP PCR methods.RESULTSThis study revealed a substantial change in the expression of several genes associated with cancer-promoting biological processes including viral processes, immune response, cell-death, cell-proliferation, different signaling pathways, etc. Additionally, promoter analysis through in silico mode revealed that a total of 32.7% of genes possess BRN3A binding sites at their promoters. Physical interaction of BRN3A with IFITM1, OAS3, ISG15, BCL2L1 and HSP90AB1 genes was also confirmed.CONCLUSIONSThe present study identified molecular targets of BRN3A and provided new insight into the pathogenesis of cervical cancer. According to our knowledge, this is the first report on the effect on eukaryotic transcriptomes after over-expression and knocking down BRN3A.

2025-03-01·Diagnostic Microbiology and Infectious Disease

Heterogeneity of OAS family expression in tuberculosis and the impact of different sample selection: a comprehensive analysis

Article

作者: Zhu, Mingzhi ; Peng, Lijun ; Shao, Yanqin ; Zhou, Hongjuan ; Mei, Bin ; Dai, Lingshan

The 2'-5' oligoadenylate synthetase (OAS)family, comprising OAS1, OAS2, OAS3, and OASL, has been shown to participate in the host immune response against Mycobacterium tuberculosis (Mtb). However, their expression profiles in tuberculosis (TB) remain inconsistent. In two TB-related datasets, the OAS family exhibits contrasting expression trends. To further investigate, we examined the expression of the OAS family in whole blood, peripheral blood mononuclear cells (PBMC), and pleural fluid mononuclear cells (PFMC) as study samples, focusing on pulmonary tuberculosis (PTB) and tuberculous pleuritis (TPE). The results revealed differing expression patterns of the OAS family in the two diseases. In PFMC samples from TPE patients, the OAS family showed overall upregulation. Additionally, matched samples from nine TPE patients indicated overlapping expression of the OAS family in both PBMC and PFMC samples.

2025-02-19·Journal of Agricultural and Food Chemistry

Casein Glycomacropeptide Regulates Gene Expression in Intestinal Epithelial Cells: Effect of Simulated Gastrointestinal Digestion and Peptide Microencapsulation

Article

作者: Tena-Garitaonaindia, Mireia ; Cian, Raúl E. ; Sánchez de Medina, Fermín ; Martínez-Augustin, Olga

κ-Casein glycomacropeptide (GMP) exerts anti-inflammatory and immune modulatory effects. A bovine GMP concentrate and its in vitro digestion product were obtained. GMP was also microencapsulated with phycocolloids and further digested. These products were tested in three-dimensional (3D) and open monolayer two-dimensional (2D) mouse jejunal organoids. Almost no effect was observed on the 2D organoids. In 3D organoids, GMP induced intestinal proliferation (Axin2, Pcna) and differentiation (Vil1, Alpl) genes together with Muc3, antibacterial genes (Lyz1, Pla2g2a), and Cxcl1. GMP also induced interferon I defense genes (Ifnb1, Ifr3, Oas2, Oas3, Rnasel) under basal conditions and in TNF-stimulated organoids. In vitro digestion abrogated the effects of GMP and induced new genes (Lgr5, Olfm4, and Lct). In TNF-stimulated organoids, digested GMP repressed multiple genes. Encapsulation largely preserved the GMP effects. In conclusion, GMP showed differential effects in 3D and 2D organoids. The effects of digestion peptides were also different, suggesting distinct potential as functional foods.

项与 OAS3 相关的新闻（医药）

2024-02-27

·生物探索

Nat Cell Biol | β细胞保护机制的突破：m^6A甲基化在1型糖尿病中的关键作用

引言1型糖尿病(T1D)的特征是胰腺β细胞的破坏。一些观察结果重新引起了人们对β细胞RNA传感器和编辑器的兴趣。2024年2月26日，芝加哥大学何川及哈佛医学院Rohit N. Kulkarni共同通讯在Nature Cell Biology 在线发表题为“Redox regulation of m6A methyltransferase METTL3 in β-cells controls the innate immune response in type 1 diabetes”的研究论文，该研究发现N6 -甲基腺苷(m6 A)是一种适应性β-细胞保护机制，在T1D发病时控制抗病毒先天免疫反应的幅度和持续时间。m6 A“书写者”甲基转移酶3 (METTL3)水平在T1D发病时在β-细胞中急剧升高，但随着疾病进展迅速下降。m6 A测序结果显示，在T1D发病时，人胰岛和EndoC-βH1细胞中几种关键的先天免疫介质(包括OAS1、OAS2、OAS3和ADAR1)的m6 A高甲基化。METTL3沉默通过增加2 ' -5 ' -寡聚腺苷酸合成酶mRNA的稳定性来提高其水平。与此一致的是，在非肥胖糖尿病小鼠T1D模型中，延长β细胞中Mettl3过表达的体内基因治疗延迟了糖尿病的进展。从机制上讲，活性氧的积累阻止了METTL3响应细胞因子的上调，而生理水平的一氧化氮增强了METTL3的水平和活性。此外，还报道了METTL3蛋白锌指结构域C276和C326位置的半胱氨酸对S-亚硝基化敏感，并且对METTL3介导的人β细胞低聚腺苷酸合成酶mRNA稳定性的调节很重要。总之，该研究报告了m6 A在人类T1D发病期间在β细胞水平调节先天免疫反应。区分自我与非自我DNA或RNA的能力是先天免疫系统的一项基本功能。因此，一些自身免疫性疾病是由先天免疫系统的过度激活引发的。此外，大量证据表明，在1型糖尿病(T1D)发病前，介导先天免疫系统的多个基因被激活。这一点具有重要意义，因为参与先天免疫反应的核酸传感器在T1D发病时在胰岛素胰岛中上调。上调的基因包括2 ' -5 ' -寡腺苷酸合成酶(OAS)家族，这是一类核苷酸转移酶，一旦被激活，要么独立起作用，要么产生2 ' -5 '连接的寡腺苷酸来激活RNase L。值得注意的是，OAS基因簇的多态性与T1D的易感性有关。有趣的是，β-细胞在胰岛细胞中是独一无二的，它具有上调OAS表达的能力到干扰素(IFN)-α或聚(I:C)(双链RNA (dsRNA)模拟物)。在dsRNA诱导的T1D小鼠模型中，OAS在β-细胞中的过度表达导致增殖阻滞和凋亡，而RNase L缺失的小鼠可免受糖尿病的影响，这与OAS-RNase L通路的过度激活导致β-细胞死亡和T1D14的观点一致。m6 A是信使RNA中最丰富的修饰。腺苷甲基化水平由甲基转移酶3 (METTL3)和14 (METTL14)等“书写”蛋白调节。几种RNA结合蛋白，“阅读器”，包括YT521-B同源家族蛋白(例如，YTHDF)，识别甲基化腺苷并调节mRNA生物学的几个方面，包括mRNA衰变。METTL3是m6 A书写复合物中唯一具有催化活性的酶。最近的研究表明，METTL3的活性可以通过SUMOylation和磷酸化来调节。然而，半胱氨酸氧化修饰如S-亚硝基化(SNO)的作用尚未被探索。SNO在控制METTL3功能和OAS mRNA衰变中的作用（Credit: Nature Cell Biology）最近的发现表明，m6 A机制通过促进腺苷向肌苷(A-to-I) RNA编辑调节ADAR1或阻断内源性异常dsRNAs的合成的转变，加速成纤维细胞中I型IFN基因的周转，从而调节先天免疫反应。然而，m6 A在T1D中的生物学作用，更具体地说，它们对介导β细胞先天免疫反应的贡献尚不清楚。该研究发现METTL3水平在T1D发病时升高，然后迅速下降。此外，OAS基因的m6 A高甲基化，并证明了METTL3在人pseudoislets 和EndoC-βH1细胞中的下调会导致OAS蛋白的上调。还观察到，m6 A通过氧化还原敏感的METTL3锌指结构域的半胱氨酸残基(C276和C326)的SNO加速了OAS mRNA的衰变。β细胞中Mettl3的持续过表达能够限制Oas的上调，并保护非肥胖糖尿病(NOD)小鼠模型的T1D不发生糖尿病，这支持了这些发现的翻译意义。该研究确定了m6 A作为一种适应性β细胞保护机制，在T1D发病时控制先天抗病毒免疫反应。原文链接https://www.nature.com/articles/s41556-024-01368-0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Nature | 癌症与神经系统的致命舞蹈

信使RNA基因疗法

分析

对领域进行一次全面的分析。

或

查看完整样例数据

生物医药百科问答

全新生物医药AI Agent 覆盖科研全链路，让突破性发现快人一步

立即开始免费试用!

智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台，助您全方位提升您的研发与决策效率。

立即开始数据试用!

智慧芽新药库数据也通过智慧芽数据服务平台，以API或者数据包形式对外开放，助您更加充分利用智慧芽新药情报信息。