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RNA-binding proteins in autoimmunity: From genetics to molecular biology. 自身免疫中的 RNA 结合蛋白:从遗传学到分子生物学
IF 7.3 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-07-01 Epub Date: 2023-01-19 DOI: 10.1002/wrna.1772
Valeria Lodde, Matteo Floris, Enrico Zoroddu, Ignazio Roberto Zarbo, Maria Laura Idda

Autoimmune diseases (ADs) are chronic pathologies generated by the loss of immune tolerance to the body's own cells and tissues. There is growing recognition that RNA-binding proteins (RBPs) critically govern immunity in healthy and pathological conditions by modulating gene expression post-transcriptionally at all levels: nuclear mRNA splicing and modification, export to the cytoplasm, as well as cytoplasmic mRNA transport, storage, editing, stability, and translation. Despite enormous efforts to identify new therapies for ADs, definitive solutions are not yet available in many instances. Recognizing that many ADs have a strong genetic component, we have explored connections between the molecular biology and the genetics of RBPs in ADs. Here, we review the genetics and molecular biology of RBPs in four major ADs, multiple sclerosis (MS), type 1 diabetes mellitus (T1D), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). We anticipate that gaining insights into the genetics and biology of ADs can facilitate the discovery of new therapies. This article is categorized under: RNA in Disease and Development > RNA in Disease.

自身免疫性疾病(ADs)是由于机体对自身细胞和组织失去免疫耐受而导致的慢性病变。越来越多的人认识到,RNA 结合蛋白(RBPs)通过在转录后各级调节基因表达:核 mRNA 剪接和修饰、向细胞质输出以及细胞质 mRNA 运输、储存、编辑、稳定性和翻译,对健康和病理状态下的免疫起着至关重要的作用。尽管人们为找到治疗注意力缺失症的新疗法付出了巨大努力,但在许多情况下,仍无法找到确切的解决方案。我们认识到许多注意力缺失症都有很强的遗传因素,因此我们探索了注意力缺失症中 RBPs 分子生物学和遗传学之间的联系。在此,我们回顾了四种主要注意力缺失症、多发性硬化症(MS)、1 型糖尿病(T1D)、系统性红斑狼疮(SLE)和类风湿性关节炎(RA)中 RBPs 的遗传学和分子生物学。我们预计,深入了解注意力缺失症的遗传学和生物学特性将有助于发现新的疗法。本文归类于疾病与发育中的 RNA > 疾病中的 RNA。
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引用次数: 0
Exploring the structure, function of thiamine pyrophosphate riboswitch, and designing small molecules for antibacterial activity. 探索焦磷酸硫胺素核糖开关的结构和功能,设计具有抗菌活性的小分子。
IF 7.3 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-07-01 Epub Date: 2023-01-02 DOI: 10.1002/wrna.1774
Padmaja D Wakchaure, Bishwajit Ganguly

During the last decade, riboswitches emerged as new small-molecule sensing RNA in bacteria. Thiamine pyrophosphate (TPP) riboswitch is widely distributed and occurs in plants, bacteria, fungi, and archaea. Extensive biochemical, structural, and genetic studies have been carried out to elucidate the recognition mechanism of TPP riboswitches. However, a comprehensive report summarizing all information on recognition principles and newly designed ligands for TPP riboswitch is scarce in the literature. This review gives a comprehensive understanding of the TPP riboswitch's structure, mechanism, and methods applied to design ligands for the TPP riboswitch. The ligand-bound TPP riboswitch was studied with various experimental and theoretical techniques to elucidate the conformational dynamics. The mutation studies shed light on the significance of pyrimidine sensing helix for the binding of ligands. Further, the structure-activity relationship study and fragment-based approach lead to the development of ligands with Kd values at the sub-micromolar level. However, there is a need to design more potent inhibitors for TPP riboswitch for therapeutic applications. The recent advancements in ligand design highlight the TPP riboswitch as a promising target for developing new antibiotics. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Riboswitches Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.

过去十年间,核糖开关作为新的小分子传感 RNA 出现在细菌中。焦磷酸硫胺素(TPP)核糖开关广泛分布于植物、细菌、真菌和古细菌中。为了阐明 TPP 核糖开关的识别机制,已经开展了广泛的生化、结构和遗传研究。然而,有关 TPP 核糖开关的识别原理和新设计配体的所有信息的综合报告在文献中并不多见。本综述全面介绍了 TPP 核糖开关的结构、机理以及用于设计 TPP 核糖开关配体的方法。通过各种实验和理论技术对配体结合的 TPP 核糖开关进行了研究,以阐明其构象动力学。突变研究揭示了嘧啶感应螺旋对配体结合的重要性。此外,通过结构-活性关系研究和基于片段的方法,开发出了 Kd 值在亚微摩级的配体。然而,还需要为 TPP 核糖开关设计更有效的抑制剂,以用于治疗。配体设计方面的最新进展凸显了 TPP 核糖开关是开发新型抗生素的一个前景广阔的靶点。本文归类于调控 RNAs/RNAi/Riboswitches > 核糖开关 调控 RNAs/RNAi/Riboswitches > 调控 RNAs。
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引用次数: 0
The Phantom Mark: Enigmatic roles of phospho-Threonine 4 modification of the C-terminal domain of RNA polymerase II. 幻影标记:RNA 聚合酶 II C 端结构域磷酸苏氨酸 4 修饰的神秘作用。
IF 6.4 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2023-07-01 Epub Date: 2023-01-06 DOI: 10.1002/wrna.1771
Ryan P Kempen, Preeti Dabas, Aseem Z Ansari

The largest subunit of RNA polymerase II (Pol II) has an unusual carboxyl-terminal domain (CTD). This domain is composed of a tandemly repeating heptapeptide, Y1 S2 P3 T4 S5 P6 S7 , that has multiple roles in regulating Pol II function and processing newly synthesized RNA. Transient phosphorylation of Ser2 and Ser5 of the YS2 PTS5 PS repeat have well-defined roles in recruiting different protein complexes and coordinating sequential steps in gene transcription. As such, these phospho-marks encipher a molecular recognition code, colloquially termed the CTD code. In contrast, the contribution of phospho-Threonine 4 (pThr4/pT4) to the CTD code remains opaque and contentious. Fuelling the debate on the relevance of this mark to gene expression are the findings that replacing Thr4 with a valine or alanine has varied impact on cellular function in different species and independent proteomic analyses disagree on the relative abundance of pThr4 marks. Yet, substitution with negatively charged residues is lethal and even benign mutations selectively disrupt synthesis and 3' processing of distinct sets of coding and non-coding transcripts. Suggestive of non-canonical roles, pThr4 marked Pol II regulates distinct gene classes in a species- and signal-responsive manner. Hinting at undiscovered roles of this elusive mark, multiple signal-responsive kinases phosphorylate Thr4 at target genes. Here, we focus on this under-explored residue and postulate that the pThr4 mark is superimposed on the canonical CTD code to selectively regulate expression of targeted genes without perturbing genome-wide transcriptional processes. This article is categorized under: RNA Processing > 3' End Processing RNA Processing > Processing of Small RNAs RNA Processing > Splicing Regulation/Alternative Splicing.

RNA 聚合酶 II(Pol II)的最大亚基有一个不同寻常的羧基末端结构域(CTD)。该结构域由串联重复的七肽 Y1 S2 P3 T4 S5 P6 S7 组成,在调节 Pol II 功能和处理新合成的 RNA 方面具有多重作用。YS2 PTS5 PS 重复序列的 Ser2 和 Ser5 的瞬时磷酸化在招募不同的蛋白质复合物和协调基因转录的连续步骤方面具有明确的作用。因此,这些磷酸标记编码了一种分子识别代码,俗称 CTD 代码。与此相反,磷酸苏氨酸 4(pThr4/pT4)对 CTD 代码的贡献仍不明确,且存在争议。在不同物种中,用缬氨酸或丙氨酸取代 Thr4 对细胞功能的影响各不相同,而独立的蛋白质组分析也对 pThr4 标记的相对丰度存在分歧,这加剧了关于该标记与基因表达相关性的争论。然而,带负电荷残基的取代是致命的,即使是良性突变也会选择性地破坏不同编码和非编码转录本的合成和 3' 处理。pThr4标记的Pol II以物种和信号响应的方式调控不同的基因类别,这表明了它的非规范作用。多种信号反应激酶在靶基因上磷酸化 Thr4,暗示了这一难以捉摸的标记尚未被发现的作用。在这里,我们将重点放在这个未被充分探索的残基上,并推测 pThr4 标记叠加在标准 CTD 代码上,在不干扰全基因组转录过程的情况下选择性地调控目标基因的表达。本文归类于RNA 处理 > 3' 端处理 RNA 处理 > 小 RNA 的处理 RNA 处理 > 剪接调节/替代剪接。
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引用次数: 0
The emerging roles of circRNAs in traits associated with livestock breeding. circRNA 在家畜育种相关性状中的新作用。
IF 7.3 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-07-01 Epub Date: 2023-01-11 DOI: 10.1002/wrna.1775
Ping Sun, Mengjie Chen, Suren R Sooranna, Deshun Shi, Qingyou Liu, Hui Li

Many indicators can be used to evaluate the productivity and quality of livestock, such as meat and milk production as well as fat deposition. Meat and milk production are measures of livestock performance, while fat deposition affects the taste and flavor of the meat. The circRNAs, are non-coding RNAs, that are involved in the regulation of all these three traits. We review the functions and mechanisms of circRNAs in muscle and fat development as well as lactation to provide a theoretical basis for circRNA research in animal husbandry. Various phenotypic changes presented in livestock may be produced by different circRNAs. Our current concern is how to use the roles played by circRNAs to our advantage to produce the best possible livestock. Hence, we describe the advantages and disadvantages of knockout techniques for circRNAs. In addition, we also put forward our thoughts regarding the mechanism and network of circRNAs to provide researchers with novel ideas of how molecular biology can help us advance our goals in animal farming. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.

许多指标可用于评估牲畜的生产率和质量,如产肉量和产奶量以及脂肪沉积。产肉量和产奶量是衡量家畜性能的指标,而脂肪沉积则会影响肉的口感和风味。circRNA 是一种非编码 RNA,参与了上述三种性状的调控。我们回顾了 circRNA 在肌肉和脂肪发育以及泌乳过程中的功能和机制,为畜牧业中的 circRNA 研究提供理论基础。家畜的各种表型变化可能是由不同的 circRNA 产生的。我们目前关心的问题是如何利用 circRNAs 发挥的作用,使其成为我们的优势,从而生产出最好的家畜。因此,我们介绍了 circRNAs 基因敲除技术的优缺点。此外,我们还就 circRNAs 的机制和网络提出了自己的想法,以便为研究人员提供分子生物学如何帮助我们实现畜牧业目标的新思路。本文归类于RNA 在疾病和发育中的作用 > RNA 在疾病中的作用 RNA 与蛋白质和其他分子的相互作用 > 蛋白质与 RNA 的相互作用:RNA 与蛋白质及其他分子的相互作用 > 蛋白质-RNA 识别 RNA 与蛋白质及其他分子的相互作用 > RNA 蛋白复合物。
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引用次数: 0
Immune dysregulation and RNA N6-methyladenosine modification in sepsis. 脓毒症的免疫失调和RNA n6 -甲基腺苷修饰。
IF 7.3 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-05-01 DOI: 10.1002/wrna.1764
Hongyan Chen, Xiaoting Zhang, Hao Su, Judeng Zeng, Hung Chan, Qing Li, Xiaodong Liu, Lin Zhang, William Ka Kei Wu, Matthew Tak Vai Chan, Huarong Chen

Sepsis is defined as life-threatening organ dysfunction caused by the host immune dysregulation to infection. It is a highly heterogeneous syndrome with complex pathophysiological mechanisms. The host immune response to sepsis can be divided into hyper-inflammatory and immune-suppressive phases which could exist simultaneously. In the initial stage, systemic immune response is activated after exposure to pathogens. Both innate and adaptive immune cells undergo epigenomic, transcriptomic, and functional reprogramming, resulting in systemic and persistent inflammatory responses. Following the hyper-inflammatory phase, the body is in a state of continuous immunosuppression, which is related to immune cell apoptosis, metabolic failure, and epigenetic reprogramming. Immunosuppression leads to increased susceptibility to secondary infections in patients with sepsis. RNA N6-Methyladenosine (m6A) has been recognized as an indispensable epitranscriptomic modification involved in both physiological and pathological processes. Recent studies suggest that m6A could reprogram both innate and adaptive immune cells through posttranscriptional regulation of RNA metabolism. Dysregulated m6A modifications contribute to the pathogenesis of immune-related diseases. In this review, we summarize immune cell changes and the potential role of m6A modification in sepsis. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > RNA Editing and Modification.

脓毒症被定义为由宿主对感染免疫失调引起的危及生命的器官功能障碍。它是一种高度异质性的综合征,具有复杂的病理生理机制。宿主对脓毒症的免疫反应可分为高炎症期和免疫抑制期,两者可同时存在。在初始阶段,全身免疫反应在接触病原体后被激活。先天和适应性免疫细胞都经历表观基因组、转录组和功能重编程,导致系统性和持续性炎症反应。在高炎症期之后,机体处于持续的免疫抑制状态,这与免疫细胞凋亡、代谢衰竭和表观遗传重编程有关。免疫抑制导致脓毒症患者继发感染易感性增加。RNA n6 -甲基腺苷(m6A)已被认为是参与生理和病理过程中不可或缺的外转录组修饰。最近的研究表明,m6A可以通过转录后调控RNA代谢对先天免疫细胞和适应性免疫细胞进行重编程。失调的m6A修饰有助于免疫相关疾病的发病机制。在这篇综述中,我们总结免疫细胞的变化和m6A修饰在脓毒症中的潜在作用。本文分类为:RNA在疾病和发展> RNA在疾病中的RNA加工> RNA编辑和修饰。
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引用次数: 4
Alternative splicing in bladder cancer: potential strategies for cancer diagnosis, prognosis, and treatment. 膀胱癌的选择性剪接:癌症诊断、预后和治疗的潜在策略。
IF 7.3 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-05-01 DOI: 10.1002/wrna.1760
Antonio J Montero-Hidalgo, Jesús M Pérez-Gómez, Antonio J Martínez-Fuentes, Enrique Gómez-Gómez, Manuel D Gahete, Juan M Jiménez-Vacas, Raúl M Luque
Bladder cancer is the most common malignancy of the urinary tract worldwide. The therapeutic options to tackle this disease comprise surgery, intravesical or systemic chemotherapy, and immunotherapy. Unfortunately, a wide number of patients ultimately become resistant to these treatments and develop aggressive metastatic disease, presenting a poor prognosis. Therefore, the identification of novel therapeutic approaches to tackle this devastating pathology is urgently needed. However, a significant limitation is that the progression and drug response of bladder cancer is strongly associated with its intrinsic molecular heterogeneity. In this sense, RNA splicing is recently gaining importance as a critical hallmark of cancer since can have a significant clinical value. In fact, a profound dysregulation of the splicing process has been reported in bladder cancer, especially in the expression of certain key splicing variants and circular RNAs with a potential clinical value as diagnostic/prognostic biomarkers or therapeutic targets in this pathology. Indeed, some authors have already evidenced a profound antitumor effect by targeting some splicing factors (e.g., PTBP1), mRNA splicing variants (e.g., PKM2, HYAL4‐v1), and circular RNAs (e.g., circITCH, circMYLK), which illustrates new possibilities to significantly improve the management of this pathology. This review represents the first detailed overview of the splicing process and its alterations in bladder cancer, and highlights opportunities for the development of novel diagnostic/prognostic biomarkers and their clinical potential for the treatment of this devastating cancer type.
膀胱癌是世界范围内最常见的泌尿系统恶性肿瘤。治疗方法包括手术、膀胱内或全身化疗和免疫治疗。不幸的是,大量患者最终对这些治疗产生耐药性,并发展为侵袭性转移性疾病,预后不良。因此,迫切需要确定新的治疗方法来解决这种毁灭性的病理。然而,一个重要的限制是膀胱癌的进展和药物反应与其内在的分子异质性密切相关。从这个意义上说,由于RNA剪接具有重要的临床价值,它作为癌症的一个关键标志最近变得越来越重要。事实上,在膀胱癌中,剪接过程的严重失调已经被报道,特别是在某些关键剪接变异体和环状rna的表达中,这些剪接变异体和环状rna具有潜在的临床价值,可以作为诊断/预后生物标志物或治疗靶点。事实上,一些作者已经通过靶向一些剪接因子(如PTBP1), mRNA剪接变体(如PKM2, HYAL4-v1)和环状rna(如circITCH, circMYLK)证明了深刻的抗肿瘤作用,这表明了显著改善这种病理管理的新可能性。这篇综述首次详细概述了膀胱癌的剪接过程及其改变,并强调了开发新的诊断/预后生物标志物及其治疗这种毁灭性癌症类型的临床潜力的机会。本文分类如下:RNA加工>剪接调控/疾病和发展中的选择性剪接RNA >疾病中的RNA。
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引用次数: 1
Noncoding RNAs in oral cancer. 口腔癌中的非编码 RNA。
IF 7.3 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-05-01 Epub Date: 2022-08-12 DOI: 10.1002/wrna.1754
Jaikrishna Balakittnen, Chameera Ekanayake Weeramange, Daniel F Wallace, Pascal H G Duijf, Alexandre S Cristino, Liz Kenny, Sarju Vasani, Chamindie Punyadeera

Oral cancer (OC) is the most prevalent subtype of cancer arising in the head and neck region. OC risk is mainly attributed to behavioral risk factors such as exposure to tobacco and excessive alcohol consumption, and a lesser extent to viral infections such as human papillomaviruses and Epstein-Barr viruses. In addition to these acquired risk factors, heritable genetic factors have shown to be associated with OC risk. Despite the high incidence, biomarkers for OC diagnosis are lacking and consequently, patients are often diagnosed in advanced stages. This delay in diagnosis is reflected by poor overall outcomes of OC patients, where 5-year overall survival is around 50%. Among the biomarkers proposed for cancer detection, noncoding RNA (ncRNA) can be considered as one of the most promising categories of biomarkers due to their role in virtually all cellular processes. Similar to other cancer types, changes in expressions of ncRNAs have been reported in OC and a number of ncRNAs have diagnostic, prognostic, and therapeutic potential. Moreover, some ncRNAs are capable of regulating gene expression by various mechanisms. Therefore, elucidating the current literature on the four main types of ncRNAs namely, microRNA, lncRNA, snoRNA, piwi-RNA, and circular RNA in the context of OC pathogenesis is timely and would enable further improvements and innovations in diagnosis, prognosis, and treatment of OC. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.

口腔癌(OC)是头颈部最常见的癌症亚型。口腔癌风险主要归因于行为风险因素,如吸烟和过度饮酒,其次是病毒感染,如人类乳头状瘤病毒和爱泼斯坦-巴氏病毒。除了这些获得性风险因素外,遗传因素也与卵巢癌风险有关。尽管卵巢癌的发病率很高,但目前还缺乏诊断卵巢癌的生物标志物,因此患者往往在晚期才被诊断出来。OC患者的总体预后较差,5年总生存率约为50%,这反映了诊断的延误。在建议用于癌症检测的生物标记物中,非编码 RNA(ncRNA)可被视为最有前景的生物标记物类别之一,因为它们在几乎所有细胞过程中都发挥作用。与其他癌症类型类似,有报道称非编码 RNA 在肿瘤细胞中的表达也发生了变化,而且一些非编码 RNA 具有诊断、预后和治疗的潜力。此外,一些 ncRNA 还能通过各种机制调节基因表达。因此,阐明目前关于四种主要 ncRNA(即 microRNA、lncRNA、snoRNA、piwi-RNA 和 circular RNA)在 OC 发病机制中的作用的文献十分及时,这将有助于进一步改进和创新 OC 的诊断、预后和治疗。本文归类于RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development。
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引用次数: 0
mRNA isoform balance in neuronal development and disease. 神经元发育和疾病中的 mRNA 同工酶平衡
IF 7.3 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-05-01 Epub Date: 2022-09-19 DOI: 10.1002/wrna.1762
Geneva R LaForce, Polyxeni Philippidou, Ashleigh E Schaffer

Balanced mRNA isoform diversity and abundance are spatially and temporally regulated throughout cellular differentiation. The proportion of expressed isoforms contributes to cell type specification and determines key properties of the differentiated cells. Neurons are unique cell types with intricate developmental programs, characteristic cellular morphologies, and electrophysiological potential. Neuron-specific gene expression programs establish these distinctive cellular characteristics and drive diversity among neuronal subtypes. Genes with neuron-specific alternative processing are enriched in key neuronal functions, including synaptic proteins, adhesion molecules, and scaffold proteins. Despite the similarity of neuronal gene expression programs, each neuronal subclass can be distinguished by unique alternative mRNA processing events. Alternative processing of developmentally important transcripts alters coding and regulatory information, including interaction domains, transcript stability, subcellular localization, and targeting by RNA binding proteins. Fine-tuning of mRNA processing is essential for neuronal activity and maintenance. Thus, the focus of neuronal RNA biology research is to dissect the transcriptomic mechanisms that underlie neuronal homeostasis, and consequently, predispose neuronal subtypes to disease. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.

在整个细胞分化过程中,mRNA 同工酶的多样性和丰度在空间和时间上都受到调控。表达同工酶的比例有助于细胞类型的分化,并决定分化细胞的关键特性。神经元是一种独特的细胞类型,具有复杂的发育程序、特征性细胞形态和电生理潜能。神经元特异性基因表达程序确立了这些独特的细胞特征,并推动了神经元亚型的多样性。具有神经元特异性替代加工的基因富含神经元的关键功能,包括突触蛋白、粘附分子和支架蛋白。尽管神经元基因表达程序具有相似性,但每个神经元亚类都可以通过独特的 mRNA 替代加工事件加以区分。对发育具有重要意义的转录本的替代加工会改变编码和调控信息,包括相互作用域、转录本稳定性、亚细胞定位以及 RNA 结合蛋白的靶向性。mRNA 加工的微调对神经元的活动和维持至关重要。因此,神经元 RNA 生物学研究的重点是剖析神经元稳态的转录组机制,进而确定神经元亚型的疾病倾向。本文归类于疾病与发育中的 RNA > 疾病中的 RNA 疾病与发育中的 RNA > 发育中的 RNA。
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引用次数: 0
Insights into established and emerging roles of SR protein family in plants and animals. SR蛋白家族在植物和动物中已建立的和新兴的作用。
IF 7.3 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-05-01 DOI: 10.1002/wrna.1763
Kundan Kumar, Shubham Kumar Sinha, Upasana Maity, Pulugurtha Bharadwaja Kirti, Koppolu Raja Rajesh Kumar

Splicing of pre-mRNA is an essential part of eukaryotic gene expression. Serine-/arginine-rich (SR) proteins are highly conserved RNA-binding proteins present in all metazoans and plants. SR proteins are involved in constitutive and alternative splicing, thereby regulating the transcriptome and proteome diversity in the organism. In addition to their role in splicing, SR proteins are also involved in mRNA export, nonsense-mediated mRNA decay, mRNA stability, and translation. Due to their pivotal roles in mRNA metabolism, SR proteins play essential roles in normal growth and development. Hence, any misregulation of this set of proteins causes developmental defects in both plants and animals. SR proteins from the animal kingdom are extensively studied for their canonical and noncanonical functions. Compared with the animal kingdom, plant genomes harbor more SR protein-encoding genes and greater diversity of SR proteins, which are probably evolved for plant-specific functions. Evidence from both plants and animals confirms the essential role of SR proteins as regulators of gene expression influencing cellular processes, developmental stages, and disease conditions. This article is categorized under: RNA Processing > Splicing Mechanisms RNA Processing > Splicing Regulation/Alternative Splicing.

前体mrna的剪接是真核生物基因表达的重要组成部分。富丝氨酸/精氨酸(SR)蛋白是存在于所有后生动物和植物中的高度保守的rna结合蛋白。SR蛋白参与构成剪接和选择性剪接,从而调节生物体的转录组和蛋白质组多样性。除了剪接作用外,SR蛋白还参与mRNA输出、无义介导的mRNA衰变、mRNA稳定性和翻译。SR蛋白在mRNA代谢中起关键作用,在正常生长发育中起重要作用。因此,这组蛋白质的任何失调都会导致植物和动物的发育缺陷。来自动物王国的SR蛋白因其规范和非规范功能而被广泛研究。与动物界相比,植物基因组中含有更多的SR蛋白编码基因和更大的SR蛋白多样性,这可能是为植物特异性功能而进化的。来自植物和动物的证据证实了SR蛋白作为影响细胞过程、发育阶段和疾病状况的基因表达调节剂的重要作用。本文分类如下:RNA加工>剪接机制RNA加工>剪接调控/选择性剪接。
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引用次数: 5
The emerging roles of CFIm25 (NUDT21/CPSF5) in human biology and disease. CFIm25(NUDT21/CPSF5)在人类生物学和疾病中的新作用。
IF 7.3 2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-05-01 Epub Date: 2022-08-14 DOI: 10.1002/wrna.1757
Chioniso Patience Masamha

The mammalian cleavage factor I subunit CFIm25 (NUDT21) binds to the UGUA sequences of precursor RNAs. Traditionally, CFIm25 is known to facilitate 3' end formation of pre-mRNAs resulting in the formation of polyadenylated transcripts. Recent studies suggest that CFIm25 may be involved in the cyclization and hence generation of circular RNAs (circRNAs) that contain UGUA motifs. These circRNAs act as competing endogenous RNAs (ceRNAs) that disrupt the ceRNA-miRNA-mRNA axis. Other emerging roles of CFIm25 include regulating both alternative splicing and alternative polyadenylation (APA). APA generates different sized transcripts that may code for different proteins, or more commonly transcripts that code for the same protein but differ in the length and sequence content of their 3' UTRs (3' UTR-APA). CFIm25 mediated global changes in 3' UTR-APA affect human physiology including spermatogenesis and the determination of cell fate. Deregulation of CFIm25 and changes in 3' UTR-APA have been implicated in several human diseases including cancer. In many cancers, CFIm25 acts as a tumor suppressor. However, there are some cancers where CFIm25 has the opposite effect. Alterations in CFIm25-driven 3' UTR-APA may also play a role in neural dysfunction and fibrosis. CFIm25 mediated 3' UTR-APA changes can be used to generate specific signatures that can be used as potential biomarkers in development and disease. Due to the emerging role of CFIm25 as a regulator of the aforementioned RNA processing events, modulation of CFIm25 levels may be a novel viable therapeutic approach. This article is categorized under: RNA Processing > 3' End Processing RNA in Disease and Development > RNA in Disease.

哺乳动物裂解因子 I 亚基 CFIm25(NUDT21)与前体 RNA 的 UGUA 序列结合。传统上,CFIm25 被认为能促进前体 mRNA 的 3' 端形成,从而形成多聚腺苷酸转录本。最近的研究表明,CFIm25 可能参与了含有 UGUA 基序的环状 RNA(circRNA)的环化和生成。这些环状 RNA 可作为竞争性内源性 RNA(ceRNA),破坏 ceRNA-miRNA-mRNA 轴。CFIm25 的其他新作用包括调节替代剪接和替代多腺苷酸化(APA)。APA 生成不同大小的转录本,这些转录本可能编码不同的蛋白质,或者更常见的是编码相同蛋白质但其 3' UTR 的长度和序列内容不同的转录本(3' UTR-APA)。CFIm25 介导的 3' UTR-APA 全局变化会影响人类生理,包括精子发生和细胞命运的决定。CFIm25 的失调和 3' UTR-APA 的变化与包括癌症在内的多种人类疾病有关。在许多癌症中,CFIm25 是一种肿瘤抑制因子。然而,在某些癌症中,CFIm25却具有相反的作用。CFIm25驱动的3' UTR-APA的改变也可能在神经功能障碍和纤维化中发挥作用。CFIm25介导的3' UTR-APA变化可用于生成特异性特征,这些特征可用作发育和疾病中的潜在生物标志物。由于CFIm25在上述RNA加工事件中扮演着新的调控角色,因此调节CFIm25的水平可能是一种新的可行的治疗方法。本文归类于RNA 加工 > 3' 端加工 RNA 在疾病和发育中的作用 > RNA 在疾病中的作用。
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引用次数: 0
期刊
Wiley Interdisciplinary Reviews: RNA
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