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Translational control of papillomavirus mRNAs in the spotlight. 聚光灯下的乳头瘤病毒 mRNA 翻译控制。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-27 DOI: 10.1016/j.tcb.2024.07.001
Alejandra García, Giovanna Maldonado, Greco Hernández

High-risk human papillomaviruses (HPVs) cause most cases of cervical cancer, a disease with an increasing impact worldwide. Recent studies have shown that the synthesis of viral oncoproteins is strongly subject to translational control. Thus, targeting the protein synthesis machinery might open novel avenues to develop innovative therapies aiming to improve patients' survival.

高危人乳头瘤病毒(HPV)是导致大多数宫颈癌病例的原因,这种疾病对全世界的影响越来越大。最近的研究表明,病毒癌蛋白的合成在很大程度上受制于翻译控制。因此,以蛋白质合成机制为靶点可能会为开发创新疗法开辟新的途径,从而提高患者的生存率。
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引用次数: 0
Membrane remodeling and trafficking piloted by SARS-CoV-2. 由 SARS-CoV-2 主导的膜重塑和贩运。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-01-22 DOI: 10.1016/j.tcb.2023.12.006
Maria Concetta Sergio, Simona Ricciardi, Andrea M Guarino, Laura Giaquinto, Maria Antonietta De Matteis

The molecular mechanisms underlying SARS-CoV-2 host cell invasion and life cycle have been studied extensively in recent years, with a primary focus on viral entry and internalization with the aim of identifying antiviral therapies. By contrast, our understanding of the molecular mechanisms involved in the later steps of the coronavirus life cycle is relatively limited. In this review, we describe what is known about the host factors and viral proteins involved in the replication, assembly, and egress phases of SARS-CoV-2, which induce significant host membrane rearrangements. We also discuss the limits of the current approaches and the knowledge gaps still to be addressed.

近年来,人们对 SARS-CoV-2 宿主细胞入侵和生命周期的分子机制进行了广泛的研究,主要侧重于病毒的进入和内化,目的是确定抗病毒疗法。相比之下,我们对冠状病毒生命周期后期所涉及的分子机制的了解相对有限。在这篇综述中,我们描述了参与 SARS-CoV-2 复制、组装和排出阶段的宿主因子和病毒蛋白的已知情况,这些阶段会引起宿主膜的显著重排。我们还讨论了目前研究方法的局限性以及有待解决的知识空白。
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引用次数: 0
Metabolic regulation of mRNA splicing. mRNA 剪接的代谢调节。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-03-01 DOI: 10.1016/j.tcb.2024.02.002
Haissi Cui, Qingyu Shi, Colette Maya Macarios, Paul Schimmel

Alternative mRNA splicing enables the diversification of the proteome from a static genome and confers plasticity and adaptiveness on cells. Although this is often explored in development, where hard-wired programs drive the differentiation and specialization, alternative mRNA splicing also offers a way for cells to react to sudden changes in outside stimuli such as small-molecule metabolites. Fluctuations in metabolite levels and availability in particular convey crucial information to which cells react and adapt. We summarize and highlight findings surrounding the metabolic regulation of mRNA splicing. We discuss the principles underlying the biochemistry and biophysical properties of mRNA splicing, and propose how these could intersect with metabolite levels. Further, we present examples in which metabolites directly influence RNA-binding proteins and splicing factors. We also discuss the interplay between alternative mRNA splicing and metabolite-responsive signaling pathways. We hope to inspire future research to obtain a holistic picture of alternative mRNA splicing in response to metabolic cues.

另类 mRNA 剪接使蛋白质组从静态基因组中多样化,并赋予细胞可塑性和适应性。在发育过程中,硬连线程序会驱动细胞的分化和特化,尽管人们经常在发育过程中探讨这一点,但替代 mRNA 剪接也为细胞提供了一种方法,使其能够对外界刺激(如小分子代谢物)的突然变化做出反应。代谢物水平和可用性的波动尤其能传递关键信息,使细胞做出反应和适应。我们总结并重点介绍了围绕 mRNA 剪接的代谢调控的研究成果。我们讨论了 mRNA 剪接的生物化学和生物物理特性的基本原理,并提出了这些原理与代谢物水平之间的相互关系。此外,我们还介绍了代谢物直接影响 RNA 结合蛋白和剪接因子的实例。我们还讨论了替代 mRNA 剪接与代谢物反应信号通路之间的相互作用。我们希望能对未来的研究有所启发,以便全面了解替代 mRNA 剪接对代谢线索的响应。
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引用次数: 0
The idiosyncrasies of oocytes. 卵细胞的特异性。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-08-13 DOI: 10.1016/j.tcb.2024.07.006
Jun Wei Pek

Animal oocytes face extreme challenges. They remain dormant in the body for long periods of time. To support offspring development and health, they need to store genetic material and maternal factors stably and at the same time manage cellular damage in a reliable manner. Recent studies have provided new insights on how oocytes cope with such challenges. This review discusses the many unusual or idiosyncratic nature of oocytes and how understanding oocyte biology can help us address issues of reproduction and intergenerational inheritance.

动物卵母细胞面临着极大的挑战。它们在体内长期处于休眠状态。为了支持后代的发育和健康,它们需要稳定地储存遗传物质和母体因子,同时以可靠的方式处理细胞损伤。最近的研究为卵母细胞如何应对这些挑战提供了新的见解。本综述将讨论卵母细胞的许多不寻常或特异性质,以及了解卵母细胞生物学如何帮助我们解决繁殖和代际遗传问题。
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引用次数: 0
Subscription and Copyright Information 订阅和版权信息
IF 19 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-08-08 DOI: 10.1016/s0962-8924(24)00151-x
No Abstract
无摘要
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引用次数: 0
Advisory Board and Contents 咨询委员会和内容
IF 19 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-08-08 DOI: 10.1016/s0962-8924(24)00148-x
No Abstract
无摘要
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引用次数: 0
Mitochondrial regulation in stem cells. 干细胞中的线粒体调节。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-08-01 Epub Date: 2023-10-31 DOI: 10.1016/j.tcb.2023.10.003
Yifei Wang, Marine Barthez, Danica Chen

Stem cells persist throughout the lifespan to repair and regenerate tissues due to their unique ability to self-renew and differentiate. Here we reflect on the recent discoveries in stem cells that highlight a mitochondrial metabolic checkpoint at the restriction point of the stem cell cycle. Mitochondrial activation supports stem cell proliferation and differentiation by providing energy supply and metabolites as signaling molecules. Concomitant mitochondrial stress can lead to loss of stem cell self-renewal and requires the surveillance of various mitochondrial quality control mechanisms. During aging, a mitochondrial protective program mediated by several sirtuins becomes dysregulated and can be targeted to reverse stem cell aging and tissue degeneration, giving hope for targeting the mitochondrial metabolic checkpoint for treating tissue degenerative diseases.

干细胞因其独特的自我更新和分化能力而在整个生命周期中持续存在,以修复和再生组织。在这里,我们回顾了最近在干细胞中的发现,这些发现突出了干细胞周期限制点的线粒体代谢检查点。线粒体激活通过提供能量供应和代谢产物作为信号分子来支持干细胞增殖和分化。伴随的线粒体应激会导致干细胞自我更新的丧失,需要监测各种线粒体质量控制机制。在衰老过程中,由几种sirtuins介导的线粒体保护程序变得失调,可以靶向逆转干细胞衰老和组织变性,为靶向线粒体代谢检查点治疗组织变性疾病带来了希望。
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引用次数: 0
Translation is an emerging constraint on protein homeostasis in ageing. 翻译是老龄化过程中蛋白质平衡的一个新的制约因素。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-02-28 DOI: 10.1016/j.tcb.2024.02.001
Jack Llewellyn, Simon J Hubbard, Joe Swift

Proteins are molecular machines that provide structure and perform vital transport, signalling and enzymatic roles. Proteins expressed by cells require tight regulation of their concentration, folding, localisation, and modifications; however, this state of protein homeostasis is continuously perturbed by tissue-level stresses. While cells in healthy tissues are able to buffer against these perturbations, for example, by expression of chaperone proteins, protein homeostasis is lost in ageing, and can lead to protein aggregation characteristic of protein folding diseases. Here, we review reports of a progressive disconnect between transcriptomic and proteomic regulation during cellular ageing. We discuss how age-associated changes to cellular responses to specific stressors in the tissue microenvironment are exacerbated by loss of ribosomal proteins, ribosomal pausing, and mistranslation.

蛋白质是提供结构并发挥重要运输、信号和酶作用的分子机器。细胞表达的蛋白质需要对其浓度、折叠、定位和修饰进行严格调节;然而,这种蛋白质平衡状态不断受到组织级压力的干扰。虽然健康组织中的细胞能够通过表达伴侣蛋白等方式缓冲这些干扰,但随着年龄的增长,蛋白质平衡会丧失,并可能导致蛋白质折叠疾病所特有的蛋白质聚集。在此,我们回顾了有关细胞老化过程中转录组和蛋白质组调控逐渐脱节的报道。我们讨论了与年龄相关的细胞对组织微环境中特定压力源的反应变化如何因核糖体蛋白的丢失、核糖体暂停和翻译错误而加剧。
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引用次数: 0
Lysosomal control of the cGAS-STING signaling. 溶酶体对 cGAS-STING 信号转导的控制。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-06 DOI: 10.1016/j.tcb.2024.05.004
Yinfeng Xu, Wei Wan

The cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway has a crucial role in combating pathogen infection. However, its aberrant activation is involved in several human disorders. Lysosomes are emerging as key negative regulators of cGAS-STING signaling. Here, we discuss the lysosomal control of cGAS-STING signaling and its implication in human disorders.

环GMP-AMP(cGAMP)合成酶(cGAS)-干扰素基因刺激器(STING)通路在对抗病原体感染方面发挥着至关重要的作用。然而,它的异常激活与多种人类疾病有关。溶酶体正在成为 cGAS-STING 信号转导的关键负调控因子。在此,我们将讨论溶酶体对 cGAS-STING 信号转导的控制及其对人类疾病的影响。
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引用次数: 0
Germline regulation of the somatic mitochondrial stress response. 种系对体细胞线粒体应激反应的调控。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-08-01 Epub Date: 2024-07-20 DOI: 10.1016/j.tcb.2024.07.004
Liankui Zhou, Ying Liu

Mitochondria are pivotal organelles for cellular energy production and the regulation of stress responses. Recent research has elucidated complex mechanisms through which mitochondrial stress in one tissue can impact distant tissues, thereby promoting overall organismal health. Two recent studies by Shen et al. and Charmpilas et al. have demonstrated that an intact germline serves as a crucial signaling hub for the activation of the somatic mitochondrial unfolded protein response (UPRmt) in Caenorhabditis elegans.

线粒体是细胞产生能量和调节应激反应的关键细胞器。最近的研究阐明了一种复杂的机制,通过这种机制,一个组织中的线粒体应激可影响远处的组织,从而促进整个机体的健康。Shen 等人和 Charmpilas 等人最近的两项研究表明,完整的种系是激活草履虫体细胞线粒体未折叠蛋白反应(UPRmt)的关键信号枢纽。
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引用次数: 0
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Trends in Cell Biology
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