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Dynamic rRNA modifications as a source of ribosome heterogeneity. 动态 rRNA 修饰是核糖体异质性的来源。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-11-04 DOI: 10.1016/j.tcb.2024.10.001
Ivan Milenkovic, Eva Maria Novoa

Ribosomal RNAs (rRNA) are the most abundant RNA molecules in almost all cell types. The general consensus in the field is that rRNA modifications are largely species-specific, with most previous works and databases solely stratifying modifications by the species of origin, without taking other levels of complexity into account. However, new evidence has emerged suggesting dynamic rRNA modifications may have additional layers of complexity and might play an important role in development and disease. In this review article, we summarize recent evidence supporting heterogeneity and dynamics in rRNA modifications in diverse biological contexts, challenging the simplistic view of 'one-species-one-rRNA-modification-pattern'. Moreover, we highlight how rRNA modification dynamics have been studied to date and how long-read sequencing methods can significantly improve our understanding of this largely unexplored yet highly abundant RNA family, across tissues, developmental stages, and diseases.

核糖体 RNA(rRNA)是几乎所有细胞类型中最丰富的 RNA 分子。该领域的普遍共识是,rRNA 的修饰在很大程度上是物种特异性的,以前的大多数研究工作和数据库都只是根据起源物种对修饰进行分层,而没有考虑其他层次的复杂性。然而,新的证据表明,动态 rRNA 修饰可能具有更多层次的复杂性,并可能在发育和疾病中发挥重要作用。在这篇综述文章中,我们总结了支持 rRNA 修饰在不同生物环境中的异质性和动态性的最新证据,对 "一种物种一种 rRNA 修饰模式 "的简单化观点提出了质疑。此外,我们还强调了迄今为止对 rRNA 修饰动态的研究情况,以及长读程测序方法如何能显著提高我们对这一在组织、发育阶段和疾病中基本未被探索但却非常丰富的 RNA 家族的认识。
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引用次数: 0
Timing is everything: advances in quantifying splicing kinetics. 时间就是一切:量化剪接动力学的进展。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-05-21 DOI: 10.1016/j.tcb.2024.03.007
Hope E Merens, Karine Choquet, Autum R Baxter-Koenigs, L Stirling Churchman

Splicing is a highly regulated process critical for proper pre-mRNA maturation and the maintenance of a healthy cellular environment. Splicing events are impacted by ongoing transcription, neighboring splicing events, and cis and trans regulatory factors on the respective pre-mRNA transcript. Within this complex regulatory environment, splicing kinetics have the potential to influence splicing outcomes but have historically been challenging to study in vivo. In this review, we highlight recent technological advancements that have enabled measurements of global splicing kinetics and of the variability of splicing kinetics at single introns. We demonstrate how identifying features that are correlated with splicing kinetics has increased our ability to form potential models for how splicing kinetics may be regulated in vivo.

剪接是一个受到高度调控的过程,对于前核糖核酸的正常成熟和维持健康的细胞环境至关重要。剪接事件受到正在进行的转录、相邻剪接事件以及相应前 mRNA 转录本上顺式和反式调控因子的影响。在这种复杂的调控环境中,剪接动力学有可能影响剪接结果,但体内研究历来具有挑战性。在这篇综述中,我们将重点介绍最近的技术进步,这些技术进步使我们能够测量全局剪接动力学和单个内含子剪接动力学的变异性。我们展示了如何通过识别与剪接动力学相关的特征来提高我们建立潜在模型的能力,以了解剪接动力学在体内是如何被调控的。
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引用次数: 0
Cytoplasmic mtDNA clearance suppresses inflammatory immune responses. 细胞质 mtDNA 清除抑制炎症免疫反应。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-10-07 DOI: 10.1016/j.tcb.2024.09.002
Chenghao Yan, Xu Liu, Haodong Xu, Liming Wang

Upon various stresses, mtDNA leaks from mitochondria into the cytoplasm, leading to cellular dysfunction and inflammation, thereby exacerbating disease progression. The autophagy-lysosome pathway has emerged as a pivotal quality control mechanism for eliminating abnormal cytoplasmic mtDNA. This article summarizes the mechanisms underlying mtDNA-triggered inflammation and how cytoplasmic mtDNA is eliminated.

在各种压力下,mtDNA 会从线粒体泄漏到细胞质中,导致细胞功能障碍和炎症,从而加剧疾病的发展。自噬-溶酶体途径已成为消除异常胞质 mtDNA 的关键质量控制机制。本文总结了mtDNA引发炎症的机制以及如何消除细胞质mtDNA。
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引用次数: 0
Epithelial metabolism as a rheostat for intestinal inflammation and malignancy. 上皮代谢是肠道炎症和恶性肿瘤的调节器。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-02-10 DOI: 10.1016/j.tcb.2024.01.004
Julian Schwärzler, Lisa Mayr, Felix Grabherr, Herbert Tilg, Timon E Adolph

The gut epithelium protects the host from a potentially hostile environment while allowing nutrient uptake that is vital for the organism. To maintain this delicate task, the gut epithelium has evolved multilayered cellular functions ranging from mucus production to hormone release and orchestration of mucosal immunity. Here, we review the execution of intestinal epithelial metabolism in health and illustrate how perturbation of epithelial metabolism affects experimental gut inflammation and tumorigenesis. We also discuss the impact of environmental factors and host-microbe interactions on epithelial metabolism in the context of inflammatory bowel disease and colorectal cancer. Insights into epithelial metabolism hold promise to unravel mechanisms of organismal health that may be therapeutically exploited in humans in the future.

肠道上皮保护宿主免受潜在敌对环境的影响,同时允许摄取对生物体至关重要的营养物质。为了完成这项微妙的任务,肠道上皮细胞进化出了多层次的细胞功能,包括粘液分泌、激素释放和协调粘膜免疫等。在此,我们回顾了肠道上皮代谢在健康中的执行情况,并说明了上皮代谢的干扰如何影响实验性肠道炎症和肿瘤发生。我们还以炎症性肠病和结直肠癌为背景,讨论了环境因素和宿主-微生物相互作用对上皮代谢的影响。对上皮代谢的深入研究有望揭示机体健康的机制,这些机制将来可能会被用于人类的治疗。
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引用次数: 0
ER remodeling via lipid metabolism. 通过脂质代谢重塑 ER。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-02-23 DOI: 10.1016/j.tcb.2024.01.011
Wonyul Jang, Volker Haucke

Unlike most other organelles found in multiple copies, the endoplasmic reticulum (ER) is a unique singular organelle within eukaryotic cells. Despite its continuous membrane structure, encompassing more than half of the cellular endomembrane system, the ER is subdivided into specialized sub-compartments, including morphological, membrane contact site (MCS), and de novo organelle biogenesis domains. In this review, we discuss recent emerging evidence indicating that, in response to nutrient stress, cells undergo a reorganization of these sub-compartmental ER domains through two main mechanisms: non-destructive remodeling of morphological ER domains via regulation of MCS and organelle hitchhiking, and destructive remodeling of specialized domains by ER-phagy. We further highlight and propose a critical role of membrane lipid metabolism in this ER remodeling during starvation.

内质网(ER)与其他大多数细胞器不同,它是真核细胞中独一无二的单一细胞器。尽管内质网具有连续的膜结构,涵盖了细胞内膜系统的一半以上,但它被细分为专门的亚区,包括形态区、膜接触位点(MCS)区和新生细胞器生物发生区。在这篇综述中,我们讨论了最近新出现的证据,这些证据表明,细胞在应对营养应激时,会通过两种主要机制对这些ER亚室域进行重组:通过调节MCS和细胞器搭便车对形态ER域进行非破坏性重塑,以及通过ER-吞噬对特化域进行破坏性重塑。我们进一步强调并提出了膜脂代谢在饥饿期间ER重塑过程中的关键作用。
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引用次数: 0
Opportunities and challenges for deep learning in cell dynamics research. 细胞动力学研究中深度学习的机遇与挑战。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2023-11-28 DOI: 10.1016/j.tcb.2023.10.010
Binghao Chai, Christoforos Efstathiou, Haoran Yue, Viji M Draviam

The growth of artificial intelligence (AI) has led to an increase in the adoption of computer vision and deep learning (DL) techniques for the evaluation of microscopy images and movies. This adoption has not only addressed hurdles in quantitative analysis of dynamic cell biological processes but has also started to support advances in drug development, precision medicine, and genome-phenome mapping. We survey existing AI-based techniques and tools, as well as open-source datasets, with a specific focus on the computational tasks of segmentation, classification, and tracking of cellular and subcellular structures and dynamics. We summarise long-standing challenges in microscopy video analysis from a computational perspective and review emerging research frontiers and innovative applications for DL-guided automation in cell dynamics research.

人工智能(AI)的发展导致越来越多地采用计算机视觉和深度学习(DL)技术来评估显微镜图像和电影。这种采用不仅解决了动态细胞生物学过程定量分析的障碍,而且开始支持药物开发、精准医学和基因组-表型图谱绘制的进步。我们调查了现有的基于人工智能的技术和工具,以及开源数据集,特别关注细胞和亚细胞结构和动态的分割,分类和跟踪的计算任务。我们从计算的角度总结了显微镜视频分析的长期挑战,并回顾了细胞动力学研究中dl引导自动化的新兴研究前沿和创新应用。
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引用次数: 0
SUMO proteases: from cellular functions to disease. SUMO 蛋白酶:从细胞功能到疾病。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-02-06 DOI: 10.1016/j.tcb.2024.01.002
Laura A Claessens, Alfred C O Vertegaal

Posttranslational modification by small ubiquitin-like modifiers (SUMOs) is critical in regulating diverse cellular processes including gene expression, cell cycle progression, genome integrity, cellular metabolism, and inflammation and immunity. The covalent attachment of SUMOs to target proteins is highly dynamic and reversible through the concerted action of SUMO conjugating and deconjugating enzymes. In mammalian cells, sentrin-specific proteases (SENPs) are the most abundant family of deconjugating enzymes. This review highlights recent advances in our knowledge of the substrates and cellular and physiological processes controlled by SENPs. Notably, SENPs are emerging as significant players in cancer, as well as in other diseases, making them attractive targets for therapeutic intervention. Consequently, a growing amount of effort in the field is being directed towards the development of SENP inhibitors.

小型泛素样修饰物(SUMOs)的翻译后修饰在调节基因表达、细胞周期进展、基因组完整性、细胞新陈代谢以及炎症和免疫等多种细胞过程中至关重要。通过 SUMO 连接酶和解连接酶的协同作用,SUMOs 与目标蛋白质的共价连接是高度动态和可逆的。在哺乳动物细胞中,中性蛋白特异性蛋白酶(SENPs)是最丰富的解结合酶家族。本综述重点介绍了我们对 SENPs 底物、细胞和生理过程控制的最新认识进展。值得注意的是,SENPs 正在成为癌症和其他疾病中的重要角色,使它们成为有吸引力的治疗干预目标。因此,该领域正致力于开发 SENP 抑制剂。
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引用次数: 0
Sugar symphony: glycosylation in cancer metabolism and stemness. 糖交响乐:癌症代谢和干细胞中的糖基化作用
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-10-26 DOI: 10.1016/j.tcb.2024.09.006
Venkatesh Varadharaj, Wyatt Petersen, Surinder K Batra, Moorthy P Ponnusamy

Glycosylation is a complex co-translational and post-translational modification (PTM) in eukaryotes that utilizes glycosyltransferases to generate a vast array of glycoconjugate structures. Recent studies have highlighted the role of glycans in regulating essential molecular, cellular, tissue, organ, and systemic biological processes with significant implications for human diseases, particularly cancer. The metabolic reliance of cancer, spanning tumor initiation, disease progression, and resistance to therapy, necessitates a range of uniquely altered cellular metabolic pathways. In addition, the intricate interplay between cell-intrinsic and -extrinsic mechanisms is exemplified by the communication between cancer cells, cancer stem cells (CSCs), cancer-associated fibroblasts (CAFs), and immune cells within the tumor microenvironment (TME). In this review article, we explore how differential glycosylation in cancer influences the metabolism and stemness features alongside new avenues in glycobiology.

在真核生物中,糖基化是一种复杂的共翻译和翻译后修饰(PTM),它利用糖基转移酶生成大量的糖共轭结构。最近的研究突显了聚糖在调节重要的分子、细胞、组织、器官和全身生物过程中的作用,对人类疾病(尤其是癌症)具有重要影响。癌症的代谢依赖性横跨肿瘤的诱发、疾病的进展和对治疗的抵抗,这就要求一系列独特的细胞代谢途径发生改变。此外,癌细胞、癌症干细胞(CSCs)、癌症相关成纤维细胞(CAFs)和肿瘤微环境(TME)中的免疫细胞之间的交流也体现了细胞内在和外在机制之间错综复杂的相互作用。在这篇综述文章中,我们将探讨癌症中的糖基化差异如何影响新陈代谢和干性特征,以及糖生物学的新途径。
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引用次数: 0
Mechanisms suppressing noncoding translation. 抑制非编码翻译的机制
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-10-22 DOI: 10.1016/j.tcb.2024.09.004
Jordan S Kesner, Xuebing Wu

The majority of the DNA sequence in our genome is noncoding and not intended for synthesizing proteins. Nonetheless, genome-wide mapping of ribosome footprints has revealed widespread translation in annotated noncoding sequences, including long noncoding RNAs (lncRNAs), untranslated regions (UTRs), and introns of mRNAs. How cells suppress the translation of potentially toxic proteins from various noncoding sequences remains poorly understood. This review summarizes mechanisms for the mitigation of noncoding translation, including the BCL2-associated athanogene 6 (BAG6)-mediated proteasomal degradation pathway, which has emerged as a unifying mechanism to suppress the translation of diverse noncoding sequences in metazoan cells.

我们基因组中的大部分 DNA 序列都是非编码序列,并非用于合成蛋白质。然而,核糖体足迹的全基因组图谱显示,已注释的非编码序列中存在广泛的翻译,包括长非编码 RNA(lncRNA)、非翻译区(UTR)和 mRNA 的内含子。细胞如何抑制来自各种非编码序列的潜在毒性蛋白质的翻译,目前仍鲜为人知。这篇综述总结了非编码翻译的缓解机制,包括 BCL2 相关athanogene 6 (BAG6) 介导的蛋白酶体降解途径,该途径已成为元动物细胞中抑制各种非编码序列翻译的统一机制。
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引用次数: 0
Extracellular vesicles from the dead: the final message. 来自死者的细胞外囊泡:最后的信息。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-10-21 DOI: 10.1016/j.tcb.2024.09.005
Bo Shi, Thanh Kha Phan, Ivan K H Poon

Communication between dying and neighbouring cells is vital to ensure appropriate processes such as tissue repair or inflammation are initiated in response to cell death. As a mechanism to aid intercellular communication, cells undergoing apoptosis can release membrane-bound extracellular vesicles (EVs) called apoptotic-cell-derived EVs (ApoEVs) that can influence downstream processes through biomolecules within or on ApoEVs. ApoEVs are broadly categorised based on size as either large ApoEVs known as apoptotic bodies (ApoBDs) or small ApoEVs (s-ApoEVs). Notably, the mechanisms of ApoBD and s-ApoEV formation are different, and the functions of these two ApoEV subsets are distinct. This Review focuses on the biogenesis and functional properties of both ApoBDs and s-ApoEVs, particularly in the context of cell clearance, cell signalling and disease progression.

凋亡细胞与邻近细胞之间的交流对于确保在细胞死亡后启动组织修复或炎症等适当过程至关重要。作为一种帮助细胞间交流的机制,发生凋亡的细胞可释放出膜结合的胞外囊泡 (EV),这种囊泡被称为凋亡细胞衍生 EV(ApoEV),可通过 ApoEV 内或 ApoEV 上的生物大分子影响下游过程。ApoEVs根据大小大致分为被称为凋亡体(ApoBDs)的大型ApoEVs和小型ApoEVs(s-ApoEVs)。值得注意的是,ApoBD 和 s-ApoEV 的形成机制不同,这两种载脂蛋白EV 亚群的功能也各不相同。本综述将重点讨论 ApoBDs 和 s-ApoEVs 的生物生成和功能特性,尤其是在细胞清除、细胞信号传导和疾病进展方面。
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引用次数: 0
期刊
Trends in Cell Biology
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