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Unveiling intracellular phase separation: advances in optical imaging of biomolecular condensates 揭示细胞内的相分离:生物分子凝聚物光学成像的进展。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.tibs.2024.06.014
Yinfeng Guo (郭寅风) , Xin Zhang (张鑫)
Intracellular biomolecular condensates, which form via phase separation, display a highly organized ultrastructure and complex properties. Recent advances in optical imaging techniques, including super-resolution microscopy and innovative microscopic methods that leverage the intrinsic properties of the molecules observed, have transcended the limitations of conventional microscopies. These advances facilitate the exploration of condensates at finer scales and in greater detail. The deployment of these emerging but sophisticated imaging tools allows for precise observations of the multiphasic organization and physicochemical properties of these condensates, shedding light on their functions in cellular processes. In this review, we highlight recent progress in methodological innovations and their profound implications for understanding the organization and dynamics of intracellular biomolecular condensates.
通过相分离形成的细胞内生物分子凝聚体显示出高度有序的超微结构和复杂的特性。光学成像技术的最新进展,包括超分辨率显微镜和利用所观察分子固有特性的创新显微方法,已经超越了传统显微镜的局限性。这些进步有助于以更精细的尺度和更详细的细节探索凝聚态。利用这些新兴而复杂的成像工具,可以精确观测这些凝聚体的多相组织和理化性质,从而揭示它们在细胞过程中的功能。在这篇综述中,我们将重点介绍方法创新的最新进展及其对理解细胞内生物分子凝聚体的组织和动力学的深远影响。
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引用次数: 0
Advisory Board and Contents 咨询委员会和内容
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 DOI: 10.1016/S0968-0004(24)00212-3
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引用次数: 0
Cytosine methylation flags mitochondrial RNA for degradation 胞嘧啶甲基化标志着线粒体 RNA 的降解。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.tibs.2024.08.001
Emeline Recazens , Alexis A. Jourdain
Mitochondrial double-stranded RNA (dsRNA) can form spontaneously in mitochondria, blocking mitochondrial gene expression and triggering an immune response. A recent study by Kim, Tan, et al. identified a safeguard mechanism in which NOP2/Sun RNA methyltransferase 4 (NSUN4)-mediated RNA methylation (m5C) recruits the RNA degradation machinery to prevent dsRNA formation.
线粒体双链 RNA(dsRNA)可在线粒体中自发形成,阻碍线粒体基因表达并引发免疫反应。Kim、Tan 等人最近的一项研究发现了一种保障机制,其中 NOP2/Sun RNA 甲基转移酶 4(NSUN4)介导的 RNA 甲基化(m5C)可招募 RNA 降解机制来防止 dsRNA 的形成。
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引用次数: 0
Subscription and Copyright Information 订阅和版权信息
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 DOI: 10.1016/S0968-0004(24)00215-9
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引用次数: 0
Ubiquitin system mutations in neurological diseases 神经系统疾病中的泛素系统突变。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.tibs.2024.06.011
Neuronal ubiquitin balance impacts the fate of countless cellular proteins, and its disruption is associated with various neurological disorders. The ubiquitin system is critical for proper neuronal cell state transitions and the clearance of misfolded or aggregated proteins that threaten cellular integrity. This article reviews the state of and recent advancements in our understanding of the disruptions to components of the ubiquitin system, in particular E3 ligases and deubiquitylases, in neurodevelopmental and neurodegenerative diseases. Specific focus is on enzymes with recent progress in their characterization, including identifying enzyme-substrate pairs, the use of stem cell and animal models, and the development of therapeutics for ubiquitin-related diseases.
神经元泛素平衡影响着无数细胞蛋白质的命运,泛素平衡的破坏与各种神经系统疾病有关。泛素系统对神经元细胞的正常状态转换以及清除威胁细胞完整性的错误折叠或聚集蛋白至关重要。这篇文章回顾了我们对泛素系统(尤其是 E3 连接酶和去泛素化酶)成分在神经发育和神经退行性疾病中的破坏的认识现状和最新进展。具体重点是最近在酶表征方面取得进展的酶,包括确定酶-底物配对、干细胞和动物模型的使用,以及泛素相关疾病疗法的开发。
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引用次数: 0
Liquid–liquid phase separation in presynaptic nerve terminals 突触前神经末梢的液-液相分离
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.tibs.2024.07.005
Jiyoung Choi , Nisha M. Rafiq , Daehun Park
The presynaptic nerve terminal is crucial for transmitting signals to the adjacent cell. To fulfill this role, specific proteins with distinct functions are concentrated in spatially confined areas within the nerve terminals. A recent concept termed liquid–liquid phase separation (LLPS) has provided new insights into how this process may occur. In this review, we aim to summarize the LLPS of proteins in different parts of the presynaptic nerve terminals, including synaptic vesicle (SV) clusters, the active zone (AZ), and the endocytic zone, with an additional focus on neurodegenerative diseases (NDDs), where the functional relevance of these properties is explored. Last, we propose new perspectives and future directions for the role of LLPS in presynaptic nerve terminals.
突触前神经末梢是向邻近细胞传递信号的关键。为了发挥这一作用,具有不同功能的特定蛋白质会集中在神经末梢内空间受限的区域。最近一种被称为液-液相分离(LLPS)的概念为这一过程如何发生提供了新的见解。在这篇综述中,我们旨在总结突触前神经末梢不同部位蛋白质的液液相分离现象,包括突触小泡(SV)簇、活性区(AZ)和内细胞区,并重点关注神经退行性疾病(NDDs),探讨这些特性的功能相关性。最后,我们就 LLPS 在突触前神经末梢中的作用提出了新的观点和未来方向。
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引用次数: 0
Beyond simple tails: poly(A) tail-mediated RNA epigenetic regulation 超越简单的尾巴:多聚(A)尾介导的 RNA 表观遗传调控。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.tibs.2024.06.013
Jingwen Liu , Falong Lu
The poly(A) tail is an essential structural component of mRNA required for the latter’s stability and translation. Recent technologies have enabled transcriptome-wide profiling of the length and composition of poly(A) tails, shedding light on their overlooked regulatory capacities. Notably, poly(A) tails contain not only adenine but also uracil, cytosine, and guanine residues. These findings strongly suggest that poly(A) tails could encode a wealth of regulatory information, similar to known reversible RNA chemical modifications. This review aims to succinctly summarize our current knowledge on the composition, dynamics, and regulatory functions of RNA poly(A) tails. Given their capacity to carry rich regulatory information beyond the genetic code, we propose the concept of ‘poly(A) tail epigenetic information’ as a new layer of RNA epigenetic regulation.
多聚(A)尾是 mRNA 的重要结构成分,是后者稳定和翻译所必需的。最近的技术实现了对整个转录组的多聚(A)尾的长度和组成的分析,从而揭示了它们被忽视的调控能力。值得注意的是,聚(A)尾不仅含有腺嘌呤,还含有尿嘧啶、胞嘧啶和鸟嘌呤残基。这些发现有力地表明,多聚(A)尾可能编码丰富的调控信息,类似于已知的可逆 RNA 化学修饰。本综述旨在简明扼要地总结我们目前对 RNA 聚(A)尾的组成、动态和调控功能的了解。鉴于 RNA 多聚(A)尾能够携带遗传密码之外的丰富调控信息,我们提出了 "多聚(A)尾表观遗传信息 "的概念,作为 RNA 表观遗传调控的一个新层次。
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引用次数: 0
UPS-dependent strategies of protein quality control degradation 依赖 UPS 的蛋白质质量控制降解策略。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.tibs.2024.06.006
The degradation of damaged proteins is critical for tissue integrity and organismal health because damaged proteins have a high propensity to form aggregates. E3 ubiquitin ligases are key regulators of protein quality control (PQC) and mediate the selective degradation of damaged proteins, a process termed ‘PQC degradation’ (PQCD). The degradation signals (degrons) that trigger PQCD are based on hydrophobic sites that are normally buried within the native protein structure. However, an open question is how PQCD-specialized E3 ligases distinguish between transiently misfolded proteins, which can be efficiently refolded, and permanently damaged proteins, which must be degraded. While significant progress has been made in characterizing degradation determinants, understanding the key regulatory signals of cellular and organismal PQCD pathways remains a challenge.
由于受损蛋白质极易形成聚集体,因此降解受损蛋白质对组织完整性和生物体健康至关重要。E3 泛素连接酶是蛋白质质量控制(PQC)的关键调控因子,介导受损蛋白质的选择性降解,这一过程被称为 "PQC 降解"(PQCD)。触发 PQCD 的降解信号(degrons)基于通常埋藏在原生蛋白质结构中的疏水位点。然而,一个悬而未决的问题是,PQCD 专化的 E3 连接酶如何区分瞬时错误折叠的蛋白质(可以有效地重新折叠)和永久受损的蛋白质(必须降解)。虽然在降解决定因素的特征描述方面取得了重大进展,但了解细胞和生物体 PQCD 途径的关键调控信号仍然是一项挑战。
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引用次数: 0
Enzoology: understanding enzyme interactions and epistasis in the cell 酶学:了解细胞中的酶相互作用和表观遗传。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 DOI: 10.1016/j.tibs.2024.07.002
Andrew Savinov
Recent work from Nguyen et al. unveils massively parallel measurements of epistatic interactions between two enzymes, dihydrofolate reductase and thymidylate synthase, in their natural cellular context. Almost 3000 mutations of DHFR in three TYMS backgrounds reveal a complex interaction network. The authors capture much of this complexity using a simple model.
Nguyen 等人的最新研究揭示了在自然细胞背景下,对二氢叶酸还原酶和胸腺嘧啶合成酶这两种酶之间的表观相互作用的大规模并行测量。三种 TYMS 背景中近 3000 个 DHFR 突变揭示了复杂的相互作用网络。作者用一个简单的模型捕捉到了这种复杂性的大部分。
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引用次数: 0
The Leishmania ribosome: more than passive mRNA translating machinery 利什曼原虫核糖体:不只是被动的 mRNA 翻译机器。
IF 11.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-01 DOI: 10.1016/j.tibs.2024.06.008

While the central dogma of molecular biology describes how genetic information flows, gene expression is also affected by epigenetic and epitranscriptomic processes. A recent report by Rajan et al. demonstrates how pseudouridylation of a Leishmania ribosomal rRNA affects the expression of particular proteins: an example of epitranslatomic control.

虽然分子生物学的核心原理是描述遗传信息如何流动,但基因表达也受到表观遗传和表观转录组过程的影响。Rajan 等人最近的一份报告展示了利什曼病核糖体 rRNA 的假苷酸化如何影响特定蛋白质的表达:这是表转录组控制的一个例子。
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引用次数: 0
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Trends in Biochemical Sciences
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