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An orthology-based methodology as a complementary approach to retrieve evolutionarily conserved A-to-I RNA editing sites. 基于同源物的方法是检索进化保守的 A 到 I RNA 编辑位点的补充方法。
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-10 DOI: 10.1080/15476286.2024.2397757
Jiyao Liu,Tianyou Zhao,Caiqing Zheng,Ling Ma,Fan Song,Li Tian,Wanzhi Cai,Hu Li,Yuange Duan
Adar-mediated adenosine-to-inosine (A-to-I) mRNA editing is a conserved mechanism that exerts diverse regulatory functions during the development, evolution, and adaptation of metazoans. The accurate detection of RNA editing sites helps us understand their biological significance. In this work, with an improved genome assembly of honeybee (Apis mellifera), we used a new orthology-based methodology to complement the traditional pipeline of (de novo) RNA editing detection. Compared to the outcome of traditional pipeline, we retrieved many novel editing sites in CDS that are deeply conserved between honeybee and other distantly related insects. The newly retrieved sites were missed by the traditional de novo identification due to the stringent criteria for controlling false-positive rate. Caste-specific editing sites are identified, including an Ile>Met auto-recoding site in Adar. This recoding was even conserved between honeybee and bumblebee, suggesting its putative regulatory role in shaping the phenotypic plasticity of eusocial Hymenoptera. In summary, we proposed a complementary approach to the traditional pipeline and retrieved several previously unnoticed CDS editing sites. From both technical and biological aspects, our works facilitate future researches on finding the functional editing sites and advance our understanding on the connection between RNA editing and the great phenotypic diversity of organisms.
Adar 介导的腺苷酸转肌苷酸(A-to-I)mRNA 编辑是一种保守的机制,在元古宙的发育、进化和适应过程中发挥着多种调控功能。准确检测 RNA 编辑位点有助于我们了解其生物学意义。在这项工作中,我们利用改进的蜜蜂(Apis mellifera)基因组组装,使用了一种新的基于选集的方法来补充传统的(从头)RNA编辑检测管道。与传统方法的结果相比,我们在蜜蜂和其他远缘昆虫之间深度保守的CDS中检索到了许多新的编辑位点。由于控制假阳性率的标准非常严格,这些新发现的位点被传统的从头鉴定所遗漏。发现了种姓特异性编辑位点,包括 Adar 中的 Ile>Met 自动重编码位点。这种重编码在蜜蜂和大黄蜂之间甚至是保守的,这表明它在塑造雌雄同体膜翅目昆虫的表型可塑性方面可能起着调控作用。总之,我们提出了一种对传统管道的补充方法,并检索到了几个以前未被注意到的 CDS 编辑位点。从技术和生物学两方面来看,我们的工作有助于未来寻找功能编辑位点的研究,并推进我们对 RNA 编辑与生物巨大表型多样性之间联系的理解。
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引用次数: 0
A systematic analysis of circRNAs in subnuclear compartments. 系统分析核下区室中的 circRNA。
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-10 DOI: 10.1080/15476286.2024.2395718
Andre Brezski,Justin Murtagh,Marcel H Schulz,Kathi Zarnack
CircRNAs are an important class of RNAs with diverse cellular functions in human physiology and disease. A thorough knowledge of circRNAs including their biogenesis and subcellular distribution is important to understand their roles in a wide variety of processes. However, the analysis of circRNAs from total RNA sequencing data remains challenging. Therefore, we developed Calcifer, a versatile workflow for circRNA annotation. Using Calcifer, we analysed APEX-Seq data to compare circRNA occurrence between whole cells, nucleus and subnuclear compartments. We generally find that circRNAs show higher abundance in whole cells compared to nuclear samples, consistent with their accumulation in the cytoplasm. The notable exception is the single-exon circRNA circCANX(9), which is unexpectedly enriched in the nucleus. In addition, we observe that circFIRRE prevails over the linear lncRNA FIRRE in both the cytoplasm and the nucleus. Zooming in on the subnuclear compartments, we show that circRNAs are strongly depleted from nuclear speckles, indicating that excess splicing factors in this compartment counteract back-splicing. Our results thereby provide valuable insights into the subnuclear distribution of circRNAs. Regarding circRNA function, we surprisingly find that the majority of all detected circRNAs possess complete open reading frames with potential for cap-independent translation. Overall, we show that Calcifer is an easy-to-use, versatile and sustainable workflow for the annotation of circRNAs which expands the repertoire of circRNA tools and allows to gain new insights into circRNA distribution and function.
CircRNA 是一类重要的 RNA,在人类生理和疾病中具有多种细胞功能。全面了解 circRNA(包括其生物发生和亚细胞分布)对于理解它们在各种过程中的作用非常重要。然而,从总 RNA 测序数据中分析 circRNAs 仍然具有挑战性。因此,我们开发了用于 circRNA 注释的多功能工作流程 Calcifer。利用 Calcifer,我们分析了 APEX-Seq 数据,比较了全细胞、细胞核和核下区室中 circRNA 的出现情况。我们普遍发现,与核样本相比,全细胞中的 circRNA 丰度更高,这与它们在细胞质中的积累一致。值得注意的例外是单外显子 circRNA circCANX(9),它意外地富集在细胞核中。此外,我们还观察到 circFIRRE 在细胞质和细胞核中都比线性 lncRNA FIRRE 占优势。放大到核下区室,我们发现circRNA在核斑点中被大量消耗,这表明该区室中过量的剪接因子抵消了反向剪接。因此,我们的研究结果为了解 circRNA 的核下分布提供了宝贵的信息。关于 circRNA 的功能,我们惊讶地发现,所有检测到的 circRNA 中,大多数都具有完整的开放阅读框,具有独立于帽子翻译的潜力。总之,我们发现 Calcifer 是一种易于使用、用途广泛且可持续的 circRNA 注释工作流程,它扩大了 circRNA 工具的范围,使我们对 circRNA 的分布和功能有了新的认识。
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引用次数: 0
Silencing LINC00663 inhibits inflammation and angiogenesis through downregulation of NR2F1 via EBF1 in bladder cancer 沉默 LINC00663 可通过下调 EBF1 抑制膀胱癌中的 NR2F1,从而抑制炎症和血管生成
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-18 DOI: 10.1080/15476286.2024.2368304
Xiulong Zhong, Lijiang Sun, Junxiang Liu, Xiaokun Yang, Minghui Hou, Xinning Wang, Huifeng Diao
This study is to elucidate the effect of the LINC00663/EBF1/NR2F1 axis on inflammation and angiogenesis in bladder cancer (BC) and related molecular mechanisms. After transfection, functional exper...
本研究旨在阐明LINC00663/EBF1/NR2F1轴对膀胱癌(BC)炎症和血管生成的影响及相关分子机制。转染后,功能实验...
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引用次数: 0
Mistranslating the genetic code with leucine in yeast and mammalian cells 在酵母和哺乳动物细胞中用亮氨酸错译遗传密码
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-04-17 DOI: 10.1080/15476286.2024.2340297
Josephine Davey-Young, Farah Hasan, Rasangi Tennakoon, Peter Rozik, Henry Moore, Peter Hall, Ecaterina Cozma, Julie Genereaux, Kyle S. Hoffman, Patricia P. Chan, Todd M. Lowe, Christopher J. Brandl, Patrick O’Donoghue
Translation fidelity relies on accurate aminoacylation of transfer RNAs (tRNAs) by aminoacyl-tRNA synthetases (AARSs). AARSs specific for alanine (Ala), leucine (Leu), serine, and pyrrolysine do no...
翻译的保真度有赖于氨基酰-tRNA 合成酶(AARS)对转移 RNA(tRNA)进行准确的氨基酰化。对丙氨酸 (Ala)、亮氨酸 (Leu)、丝氨酸和吡咯赖氨酸具有特异性的 AARSs 不...
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引用次数: 0
The regulatory roles of small nucleolar RNAs within their host locus 小核仁核糖核酸在宿主基因座内的调控作用
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-04-16 DOI: 10.1080/15476286.2024.2342685
Étienne Fafard-Couture, Stéphane Labialle, Michelle S Scott
Small nucleolar RNAs (snoRNAs) are a class of conserved noncoding RNAs forming complexes with proteins to catalyse site-specific modifications on ribosomal RNA. Besides this canonical role, several...
小核极RNA(snoRNA)是一类保守的非编码RNA,它们与蛋白质形成复合物,催化核糖体RNA上的特定位点修饰。除了这种典型作用外,还有几种...
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引用次数: 0
Synthetic RNA biology 合成 RNA 生物学
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-04-14 DOI: 10.1080/15476286.2024.2335746
Beatrix Suess
Published in RNA Biology (Vol. 21, No. 1, 2024)
发表于《RNA Biology》(第 21 卷第 1 期,2024 年)
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引用次数: 0
Global and single-nucleotide resolution detection of 7-methylguanosine in RNA 全局和单核苷酸分辨率检测 RNA 中的 7-甲基鸟苷
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-04-02 DOI: 10.1080/15476286.2024.2337493
Silvia D’Ambrosi, Raquel García-Vílchez, Darek Kedra, Patrice Vitali, Nuria Macias-Cámara, Laura Bárcena, Monika Gonzalez-Lopez, Ana M. Aransay, Sabine Dietmann, Antonio Hurtado, Sandra Blanco
RNA modifications, including N-7-methylguanosine (m7G), are pivotal in governing RNA stability and gene expression regulation. The accurate detection of internal m7G modifications is of paramount s...
包括 N-7-甲基鸟苷 (m7G) 在内的 RNA 修饰是调节 RNA 稳定性和基因表达的关键。准确检测内部的 m7G 修饰至关重要。
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引用次数: 0
MiRNAs differentially expressed in vegetative and reproductive organs of Marchantia polymorpha – insights into their expression pattern, gene structures and function 在马钱子无性器官和生殖器官中表达不同的 MiRNAs--洞察其表达模式、基因结构和功能
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-02-01 DOI: 10.1080/15476286.2024.2303555
Bharti Aggarwal, Wojciech Maciej Karlowski, Przemyslaw Nuc, Artur Jarmolowski, Zofia Szweykowska-Kulinska, Halina Pietrykowska
MicroRNAs regulate gene expression affecting a variety of plant developmental processes. The evolutionary position of Marchantia polymorpha makes it a significant model to understand miRNA-mediated...
microRNA调控影响多种植物发育过程的基因表达。Marchantia polymorpha 的进化地位使其成为了解 miRNA 介导的植物发育过程的重要模型。
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引用次数: 0
BioDeepfuse: a hybrid deep learning approach with integrated feature extraction techniques for enhanced non-coding RNA classification. BioDeepfuse:一种集成特征提取技术的混合深度学习方法,用于增强非编码 RNA 分类。
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 Epub Date: 2024-03-25 DOI: 10.1080/15476286.2024.2329451
Anderson P Avila Santos, Breno L S de Almeida, Robson P Bonidia, Peter F Stadler, Polonca Stefanic, Ines Mandic-Mulec, Ulisses Rocha, Danilo S Sanches, André C P L F de Carvalho

The accurate classification of non-coding RNA (ncRNA) sequences is pivotal for advanced non-coding genome annotation and analysis, a fundamental aspect of genomics that facilitates understanding of ncRNA functions and regulatory mechanisms in various biological processes. While traditional machine learning approaches have been employed for distinguishing ncRNA, these often necessitate extensive feature engineering. Recently, deep learning algorithms have provided advancements in ncRNA classification. This study presents BioDeepFuse, a hybrid deep learning framework integrating convolutional neural networks (CNN) or bidirectional long short-term memory (BiLSTM) networks with handcrafted features for enhanced accuracy. This framework employs a combination of k-mer one-hot, k-mer dictionary, and feature extraction techniques for input representation. Extracted features, when embedded into the deep network, enable optimal utilization of spatial and sequential nuances of ncRNA sequences. Using benchmark datasets and real-world RNA samples from bacterial organisms, we evaluated the performance of BioDeepFuse. Results exhibited high accuracy in ncRNA classification, underscoring the robustness of our tool in addressing complex ncRNA sequence data challenges. The effective melding of CNN or BiLSTM with external features heralds promising directions for future research, particularly in refining ncRNA classifiers and deepening insights into ncRNAs in cellular processes and disease manifestations. In addition to its original application in the context of bacterial organisms, the methodologies and techniques integrated into our framework can potentially render BioDeepFuse effective in various and broader domains.

非编码 RNA(ncRNA)序列的准确分类对于高级非编码基因组注释和分析至关重要,这是基因组学的一个基本方面,有助于了解 ncRNA 在各种生物过程中的功能和调控机制。虽然传统的机器学习方法已被用于区分 ncRNA,但这些方法往往需要大量的特征工程。最近,深度学习算法在 ncRNA 分类方面取得了进展。本研究提出的 BioDeepFuse 是一种混合深度学习框架,它将卷积神经网络(CNN)或双向长短期记忆(BiLSTM)网络与手工特征相结合,以提高准确性。该框架采用 k-mer one-hot、k-mer 字典和特征提取技术相结合的方法来表示输入。提取的特征嵌入深度网络后,可优化利用 ncRNA 序列的空间和序列细微差别。我们使用基准数据集和来自细菌生物体的真实世界 RNA 样本评估了 BioDeepFuse 的性能。结果显示 ncRNA 分类的准确率很高,这突出表明我们的工具在应对复杂的 ncRNA 序列数据挑战方面具有很强的鲁棒性。CNN 或 BiLSTM 与外部特征的有效结合预示着未来研究的广阔前景,尤其是在完善 ncRNA 分类器和加深对细胞过程和疾病表现中 ncRNA 的了解方面。除了最初在细菌生物体中的应用外,我们框架中集成的方法和技术有可能使 BioDeepFuse 在各种更广泛的领域中发挥有效作用。
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引用次数: 0
mRNA vaccine designs for optimal adjuvanticity and delivery. mRNA 疫苗设计,以获得最佳佐剂性和输送效果。
IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 Epub Date: 2024-03-26 DOI: 10.1080/15476286.2024.2333123
Yuki Mochida, Satoshi Uchida

Adjuvanticity and delivery are crucial facets of mRNA vaccine design. In modern mRNA vaccines, adjuvant functions are integrated into mRNA vaccine nanoparticles, allowing the co-delivery of antigen mRNA and adjuvants in a unified, all-in-one formulation. In this formulation, many mRNA vaccines utilize the immunostimulating properties of mRNA and vaccine carrier components, including lipids and polymers, as adjuvants. However, careful design is necessary, as excessive adjuvanticity and activation of improper innate immune signalling can conversely hinder vaccination efficacy and trigger adverse effects. mRNA vaccines also require delivery systems to achieve antigen expression in antigen-presenting cells (APCs) within lymphoid organs. Some vaccines directly target APCs in the lymphoid organs, while others rely on APCs migration to the draining lymph nodes after taking up mRNA vaccines. This review explores the current mechanistic understanding of these processes and the ongoing efforts to improve vaccine safety and efficacy based on this understanding.

佐剂和递送是 mRNA 疫苗设计的关键环节。在现代 mRNA 疫苗中,佐剂功能被整合到 mRNA 疫苗纳米颗粒中,从而使抗原 mRNA 和佐剂在统一的一体化配方中共同递送。在这种配方中,许多 mRNA 疫苗利用 mRNA 的免疫刺激特性和疫苗载体成分(包括脂质和聚合物)作为佐剂。然而,由于过度佐剂化和激活不适当的先天性免疫信号反而会阻碍疫苗接种效果并引发不良反应,因此必须谨慎设计。mRNA 疫苗还需要传递系统来实现淋巴器官内抗原呈递细胞 (APC) 的抗原表达。有些疫苗直接针对淋巴器官中的抗原呈递细胞,而有些则依赖于抗原呈递细胞吸收 mRNA 疫苗后迁移到引流淋巴结。本综述探讨了目前对这些过程的机理认识,以及在此基础上为提高疫苗安全性和有效性所做的不懈努力。
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引用次数: 0
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RNA Biology
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