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Small RNA-big impact: exosomal miRNAs in mitochondrial dysfunction in various diseases. 小 RNA 大影响:外泌体 miRNA 在各种疾病的线粒体功能障碍中的作用。
IF 4.1 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 Epub Date: 2024-01-04 DOI: 10.1080/15476286.2023.2293343
Xiaqing Li, Yi Han, Yu Meng, Lianghong Yin

Mitochondria are multitasking organelles involved in maintaining the cell homoeostasis. Beyond its well-established role in cellular bioenergetics, mitochondria also function as signal organelles to propagate various cellular outcomes. However, mitochondria have a self-destructive arsenal of factors driving the development of diseases caused by mitochondrial dysfunction. Extracellular vesicles (EVs), a heterogeneous group of membranous nano-sized vesicles, are present in a variety of bodily fluids. EVs serve as mediators for intercellular interaction. Exosomes are a class of small EVs (30-100 nm) released by most cells. Exosomes carry various cargo including microRNAs (miRNAs), a class of short noncoding RNAs. Recent studies have closely associated exosomal miRNAs with various human diseases, including diseases caused by mitochondrial dysfunction, which are a group of complex multifactorial diseases and have not been comprehensively described. In this review, we first briefly introduce the characteristics of EVs. Then, we focus on possible mechanisms regarding exosome-mitochondria interaction through integrating signalling networks. Moreover, we summarize recent advances in the knowledge of the role of exosomal miRNAs in various diseases, describing how mitochondria are changed in disease status. Finally, we propose future research directions to provide a novel therapeutic strategy that could slow the disease progress mediated by mitochondrial dysfunction.

线粒体是参与维持细胞平衡的多任务细胞器。线粒体除了在细胞生物能方面发挥公认的作用外,还作为信号细胞器传播各种细胞结果。然而,线粒体也有自我毁灭的因素,这些因素导致了线粒体功能障碍疾病的发生。细胞外小泡(EVs)是一类异构的膜状纳米级小泡,存在于各种体液中。细胞外小泡是细胞间相互作用的媒介。外泌体是由大多数细胞释放的一类小型 EV(30-100 纳米)。外泌体携带各种货物,包括微小核糖核酸(miRNA),这是一类短的非编码核糖核酸。最近的研究发现,外泌体 miRNA 与多种人类疾病密切相关,其中包括线粒体功能障碍引起的疾病,这些疾病是一组复杂的多因素疾病,尚未得到全面描述。在这篇综述中,我们首先简要介绍了 EVs 的特征。然后,我们重点讨论了外泌体-线粒体通过整合信号网络相互作用的可能机制。此外,我们还总结了外泌体 miRNAs 在各种疾病中作用的最新进展,描述了线粒体在疾病状态下的变化。最后,我们提出了未来的研究方向,以提供一种新的治疗策略,减缓由线粒体功能障碍介导的疾病进展。
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引用次数: 0
TBP facilitates RNA Polymerase I transcription following mitosis. TBP 有助于有丝分裂后的 RNA 聚合酶 I 转录。
IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 Epub Date: 2024-07-03 DOI: 10.1080/15476286.2024.2375097
James Z J Kwan, Thomas F Nguyen, Sheila S Teves

The TATA-box binding protein (TBP) is the sole transcription factor common in the initiation complexes of the three major eukaryotic RNA Polymerases (Pol I, II and III). Although TBP is central to transcription by the three RNA Pols in various species, the emergence of TBP paralogs throughout evolution has expanded the complexity in transcription initiation. Furthermore, recent studies have emerged that questioned the centrality of TBP in mammalian cells, particularly in Pol II transcription, but the role of TBP and its paralogs in Pol I transcription remains to be re-evaluated. In this report, we show that in murine embryonic stem cells TBP localizes onto Pol I promoters, whereas the TBP paralog TRF2 only weakly associates to the Spacer Promoter of rDNA, suggesting that it may not be able to replace TBP for Pol I transcription. Importantly, acute TBP depletion does not fully disrupt Pol I occupancy or activity on ribosomal RNA genes, but TBP binding in mitosis leads to efficient Pol I reactivation following cell division. These findings provide a more nuanced role for TBP in Pol I transcription in murine embryonic stem cells.

TATA-box 结合蛋白(TBP)是真核生物三大 RNA 聚合酶(Pol I、II 和 III)启动复合体中唯一常见的转录因子。虽然 TBP 在不同物种的三种 RNA Pols 的转录过程中起着核心作用,但在整个进化过程中出现的 TBP 旁系物增加了转录起始过程的复杂性。此外,最近的研究质疑了 TBP 在哺乳动物细胞中的中心地位,尤其是在 Pol II 转录中,但 TBP 及其旁系物在 Pol I 转录中的作用仍有待重新评估。在本报告中,我们发现在小鼠胚胎干细胞中,TBP定位在Pol I启动子上,而TBP旁系亲属TRF2仅与rDNA的间隔启动子有微弱联系,这表明它可能无法取代TBP进行Pol I转录。重要的是,急性 TBP 消耗并不会完全破坏 Pol I 在核糖体 RNA 基因上的占据或活性,但 TBP 在有丝分裂中的结合会导致 Pol I 在细胞分裂后有效地重新激活。这些发现为TBP在小鼠胚胎干细胞的Pol I转录中提供了更细致的作用。
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引用次数: 0
Transcriptional landscape of small non-coding RNAs reveals diversity of categories and functions in molluscs. 小非编码 RNA 的转录景观揭示了软体动物中类别和功能的多样性。
IF 4.1 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 Epub Date: 2024-05-01 DOI: 10.1080/15476286.2024.2348893
Songqian Huang, Kazutoshi Yoshitake, Shigeharu Kinoshita, Shuichi Asakawa

Small non-coding RNAs (sncRNAs) are non-coding RNA molecules that play various roles in metazoans. Among the sncRNAs, microRNAs (miRNAs) guide post-translational gene regulation during cellular development, proliferation, apoptosis, and differentiation, while PIWI-interacting RNAs (piRNAs) suppress transposon activity to safeguard the genome from detrimental insertion mutagenesis. While an increasing number of piRNAs are being identified in the soma and germlines of various organisms, they are scarcely reported in molluscs. To unravel the small RNA (sRNA) expression patterns and genomic function in molluscs, we generated a comprehensive sRNA dataset by sRNA sequencing (sRNA-seq) of eight mollusc species. Abundant miRNAs were identified and characterized in all investigated molluscs, and ubiquitous piRNAs were discovered in both somatic and gonadal tissues in six of the investigated molluscs, which are more closely associated with transposon silencing. Tens of piRNA clusters were also identified based on the genomic mapping results, which varied among different tissues and species. Our dataset serves as important reference data for future genomic and genetic studies on sRNAs in these molluscs and related species, especially in elucidating the ancestral state of piRNAs in bilaterians.

小非编码 RNA(sncRNA)是一种非编码 RNA 分子,在后生动物中发挥着各种作用。在 sncRNAs 中,微小 RNAs(miRNAs)在细胞发育、增殖、凋亡和分化过程中指导翻译后基因调控,而 PIWI 交互作用 RNAs(piRNAs)则抑制转座子活性,保护基因组免受有害插入突变的影响。虽然在各种生物的体细胞和种系中发现了越来越多的 piRNA,但在软体动物中却鲜有报道。为了揭示软体动物体内小 RNA(sRNA)的表达模式和基因组功能,我们通过对 8 种软体动物进行 sRNA 测序(sRNA-seq)生成了一个全面的 sRNA 数据集。在所有被研究的软体动物中,我们发现了丰富的 miRNAs,并对其进行了表征;在其中六种软体动物的体细胞和性腺组织中,我们发现了无处不在的 piRNAs,它们与转座子沉默的关系更为密切。根据基因组图谱结果还发现了数十个 piRNA 簇,这些 piRNA 簇在不同组织和物种中各不相同。我们的数据集可作为今后对这些软体动物及相关物种的 sRNAs 进行基因组学和遗传学研究的重要参考数据,特别是在阐明两栖动物中 piRNAs 的祖先状态方面。
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引用次数: 0
HNRNPD regulates the biogenesis of circRNAs and the ratio of mRNAs to circRNAs for a set of genes. HNRNPD 可调节 circRNA 的生物生成以及一组基因的 mRNA 与 circRNA 的比例。
IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 Epub Date: 2024-08-24 DOI: 10.1080/15476286.2024.2386500
Shuhui Chang, Yucong Wang, Xiaolin Wang, Hanyuan Liu, Tao Zhang, Yangge Zheng, Xueren Wang, Ge Shan, Liang Chen

Exonic circular RNAs (ecircRNAs) in animal cells are generated by backsplicing, and the biogenesis of ecircRNAs is regulated by an array of RNA binding proteins (RBPs). HNRNPD is a heterogeneous nuclear ribonucleoprotein family member with both cytoplasmic and nuclear roles, and whether HNRNPD regulates the biogenesis of circRNAs remains unknown. In this study, we examine the role of HNRNPD in the biogenesis of ecircRNAs. The levels of ecircRNAs are primarily increased upon depletion of HNRNPD. HNRNPD preferentially binds to motifs enriched with A and U nucleotides, and the flanking introns of ecircRNAs tend to have more numbers and higher intensity of HNRNPD binding sites. The levels of mRNAs are generally not significantly altered in HNRNPD knockout cells. For a small set of genes, the circRNA:mRNA ratio is substantially affected, and the mRNA levels of some of these genes demonstrate a significant decrease in HNRNPD knockout cells. CDK1 is identified as a key gene modulated by HNRNPD in the context of circRNA biogenesis. HNRNPD suppresses the biogenesis of circCDK1 and favours the generation of CDK1 mRNA, and the CDK1 protein is a critical regulator of the cell cycle and apoptosis. HNRNPD can participate in cellular physiology, including the cell cycle and apoptosis, and plays roles in clear cell renal cell carcinoma (ccRCC) by modulating circRNA biogenesis and the mRNA levels of key genes, such as CDK1.

动物细胞中的外显子环状RNA(ecircRNAs)是通过反拼接产生的,而ecircRNAs的生物发生受一系列RNA结合蛋白(RBPs)的调控。 HNRNPD是一种异质性核核糖核蛋白家族成员,具有细胞质和细胞核的双重作用,而HNRNPD是否调控circRNAs的生物发生仍是未知数。本研究探讨了 HNRNPD 在 ecircRNAs 生物发生过程中的作用。消耗 HNRNPD 后,ecircRNAs 的水平主要会增加。HNRNPD 优先与富含 A 和 U 核苷酸的基团结合,ecircRNA 的内含子侧翼往往有更多和更高强度的 HNRNPD 结合位点。在 HNRNPD 基因敲除的细胞中,mRNA 的水平一般不会发生显著变化。对于一小部分基因,circRNA:mRNA 的比例会受到很大影响,其中一些基因的 mRNA 水平在 HNRNPD 基因敲除细胞中会显著下降。CDK1 被确定为在 circRNA 生物发生过程中受 HNRNPD 调节的关键基因。HNRNPD 抑制了 circCDK1 的生物发生,有利于 CDK1 mRNA 的生成,而 CDK1 蛋白是细胞周期和细胞凋亡的关键调节因子。HNRNPD 可参与细胞生理,包括细胞周期和细胞凋亡,并通过调节 circRNA 的生物生成和 CDK1 等关键基因的 mRNA 水平,在透明细胞肾细胞癌(ccRCC)中发挥作用。
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引用次数: 0
The role of the 5' sensing function of ribonuclease E in cyanobacteria. 蓝藻中核糖核酸酶 E 的 5'感应功能的作用。
IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 Epub Date: 2024-03-12 DOI: 10.1080/15476286.2024.2328438
Ute A Hoffmann, Elisabeth Lichtenberg, Said N Rogh, Raphael Bilger, Viktoria Reimann, Florian Heyl, Rolf Backofen, Claudia Steglich, Wolfgang R Hess, Annegret Wilde

RNA degradation is critical for synchronising gene expression with changing conditions in prokaryotic and eukaryotic organisms. In bacteria, the preference of the central ribonucleases RNase E, RNase J and RNase Y for 5'-monophosphorylated RNAs is considered important for RNA degradation. For RNase E, the underlying mechanism is termed 5' sensing, contrasting to the alternative 'direct entry' mode, which is independent of monophosphorylated 5' ends. Cyanobacteria, such as Synechocystis sp. PCC 6803 (Synechocystis), encode RNase E and RNase J homologues. Here, we constructed a Synechocystis strain lacking the 5' sensing function of RNase E and mapped on a transcriptome-wide level 283 5'-sensing-dependent cleavage sites. These included so far unknown targets such as mRNAs encoding proteins related to energy metabolism and carbon fixation. The 5' sensing function of cyanobacterial RNase E is important for the maturation of rRNA and several tRNAs, including tRNAGluUUC. This tRNA activates glutamate for tetrapyrrole biosynthesis in plant chloroplasts and in most prokaryotes. Furthermore, we found that increased RNase activities lead to a higher copy number of the major Synechocystis plasmids pSYSA and pSYSM. These results provide a first step towards understanding the importance of the different target mechanisms of RNase E outside Escherichia coli.

在原核生物和真核生物中,RNA 降解对于使基因表达与不断变化的条件同步至关重要。在细菌中,中心核糖核酸酶 RNase E、RNase J 和 RNase Y 对 5'-monophosphorylated RNA 的偏好被认为是 RNA 降解的重要因素。对于 RNase E 来说,其基本机制被称为 "5'末端感应"(5's sensing),这与另一种 "直接进入"(direct entry)模式不同,后者与单磷酸化的 5'末端无关。蓝藻,如 Synechocystis sp. PCC 6803(Synechocystis),编码 RNase E 和 RNase J 同源物。在这里,我们构建了一个缺乏 RNase E 的 5'感应功能的 Synechocystis 菌株,并在整个转录组水平上绘制了 283 个依赖于 5'感应的裂解位点。这些位点包括迄今未知的目标,如编码与能量代谢和碳固定有关的蛋白质的 mRNA。蓝藻 RNase E 的 5'感应功能对 rRNA 和几种 tRNA(包括 tRNAGluUUC)的成熟非常重要。在植物叶绿体和大多数原核生物中,这种 tRNA 可激活谷氨酸进行四吡咯的生物合成。此外,我们还发现 RNase 活性的增加会导致 Synechocystis 主要质粒 pSYSA 和 pSYSM 的拷贝数增加。这些结果为了解大肠杆菌外 RNase E 不同靶机制的重要性迈出了第一步。
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引用次数: 0
Low dose ribosomal DNA P-loop mutation affects development and enforces autophagy in Arabidopsis 低剂量核糖体 DNA P 环突变影响拟南芥的生长发育并强化自噬作用
IF 4.1 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-29 DOI: 10.1080/15476286.2023.2298532
Thiruvenkadam Shanmugam, Palak Chaturvedi, Deniz Streit, Arindam Ghatak, Thorsten Bergelt, Stefan Simm, Wolfram Weckwerth, Enrico Schleiff
Arabidopsis contains hundreds of ribosomal DNA copies organized within the nucleolar organizing regions (NORs) in chromosomes 2 and 4. There are four major types of variants of rDNA, VAR1–4, based ...
拟南芥含有数百个核糖体DNA拷贝,这些拷贝组织在第2和第4号染色体的核极组织区(NORs)中。rDNA 有四种主要变体,即 VAR1-4,基于...
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引用次数: 0
Structural and computational studies of HIV-1 RNA HIV-1 RNA 的结构和计算研究
IF 4.1 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-15 DOI: 10.1080/15476286.2023.2289709
Lev Levintov, Harish Vashisth
Viruses remain a global threat to animals, plants, and humans. The type 1 human immunodeficiency virus (HIV-1) is a member of the retrovirus family and carries an RNA genome, which is reverse trans...
病毒仍然是对动物、植物和人类的全球性威胁。1 型人类免疫缺陷病毒(HIV-1)是逆转录病毒家族的一员,它携带 RNA 基因组,并通过逆转录技术将 RNA 转录成病毒。
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引用次数: 0
mRNA nuclear export: how mRNA identity features distinguish functional RNAs from junk transcripts mRNA 核输出:mRNA 身份特征如何区分功能 RNA 与垃圾转录本
IF 4.1 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-13 DOI: 10.1080/15476286.2023.2293339
Alexander F. Palazzo, Yi Qiu, Yoon Mo Kang
The division of the cellular space into nucleoplasm and cytoplasm promotes quality control mechanisms that prevent misprocessed mRNAs and junk RNAs from gaining access to the translational machiner...
将细胞空间划分为核质和细胞质可促进质量控制机制,防止处理不当的 mRNA 和垃圾 RNA 进入翻译机器。
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引用次数: 0
Therapeutic potential of natural antisense transcripts and various mechanisms involved for clinical applications and disease prevention 天然反义转录本的治疗潜力以及临床应用和疾病预防所涉及的各种机制
IF 4.1 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-13 DOI: 10.1080/15476286.2023.2293335
Ashiq Ali, Aisha Khatoon, Chenran Shao, Bilal Murtaza, Qaisar Tanveer, Zhongjing Su
Antisense transcription, a prevalent occurrence in mammalian genomes, gives rise to natural antisense transcripts (NATs) as RNA molecules. These NATs serve as agents of diverse transcriptional and ...
反义转录是哺乳动物基因组中的一种普遍现象,它产生了作为 RNA 分子的天然反义转录本(NATs)。这些反义转录本是多种转录和...
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引用次数: 0
Unraveling C-to-U RNA editing events from direct RNA sequencing 通过直接 RNA 测序揭示 C 到 U RNA 编辑事件
IF 4.1 3区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-13 DOI: 10.1080/15476286.2023.2290843
Adriano Fonzino, Caterina Manzari, Paola Spadavecchia, Uday Munagala, Serena Torrini, Silvestro Conticello, Graziano Pesole, Ernesto Picardi
In mammals, RNA editing events involve the conversion of adenosine (A) in inosine (I) by ADAR enzymes or the hydrolytic deamination of cytosine (C) in uracil (U) by the APOBEC family of enzymes, mo...
在哺乳动物中,RNA 编辑事件包括 ADAR 酶将腺苷 (A) 转化为肌苷 (I),或 APOBEC 酶家族将胞嘧啶 (C) 水解脱氨为尿嘧啶 (U)。
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引用次数: 0
期刊
RNA Biology
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