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  • The functions and unique features of long intergenic non-coding RNA
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-15
    Julia D. Ransohoff, Yuning Wei, Paul A. Khavari

    The functions and unique features of long intergenic non-coding RNAThe functions and unique features of long intergenic non-coding RNA, Published online: 15 November 2017; doi:10.1038/nrm.2017.104NatureArticleSnippet(type=short-summary, markup=Long intergenic non-coding RNAs (lincRNAs) do not overlap protein-coding genes, although some lincRNA genes have minimal coding potential and can include small open reading frames that encode functional peptides. lincRNA functions include RNA stabilization and transcription regulation and the remodelling of chromatin and genome architecture. Recent insights suggest that lincRNAs broadly serve to fine-tune the expression of neighbouring genes with remarkable tissue specificity., isJats=true)

    更新日期:2017-11-15
  • The functions and unique features of long intergenic non-coding RNA
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-15
    Julia D. Ransohoff, Yuning Wei, Paul A. Khavari

    The functions and unique features of long intergenic non-coding RNAThe functions and unique features of long intergenic non-coding RNA, Published online: 15 November 2017; doi:10.1038/nrm.2017.104NatureArticleSnippet(type=short-summary, markup=Long intergenic non-coding RNAs (lincRNAs) do not overlap protein-coding genes, although some lincRNA genes have minimal coding potential and can include small open reading frames that encode functional peptides. lincRNA functions include RNA stabilization and transcription regulation and the remodelling of chromatin and genome architecture. Recent insights suggest that lincRNAs broadly serve to fine-tune the expression of neighbouring genes with remarkable tissue specificity., isJats=true)

    更新日期:2017-11-15
  • Mechanical forces direct stem cell behaviour in development and regeneration
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-08
    Kyle H. Vining, David J. Mooney

    Stem cells and their local microenvironment, or niche, communicate through mechanical cues to regulate cell fate and cell behaviour and to guide developmental processes. During embryonic development, mechanical forces are involved in patterning and organogenesis. The physical environment of pluripotent stem cells regulates their self-renewal and differentiation. Mechanical and physical cues are also important in adult tissues, where adult stem cells require physical interactions with the extracellular matrix to maintain their potency. In vitro, synthetic models of the stem cell niche can be used to precisely control and manipulate the biophysical and biochemical properties of the stem cell microenvironment and to examine how the mode and magnitude of mechanical cues, such as matrix stiffness or applied forces, direct stem cell differentiation and function. Fundamental insights into the mechanobiology of stem cells also inform the design of artificial niches to support stem cells for regenerative therapies.

    更新日期:2017-11-08
  • Mechanobiology of collective cell behaviours
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-08
    Benoit Ladoux, René-Marc Mège

    The way in which cells coordinate their behaviours during various biological processes, including morphogenesis, cancer progression and tissue remodelling, largely depends on the mechanical properties of the external environment. In contrast to single cells, collective cell behaviours rely on the cellular interactions not only with the surrounding extracellular matrix but also with neighbouring cells. Collective dynamics is not simply the result of many individually moving blocks. Instead, cells coordinate their movements by actively interacting with each other. These mechanisms are governed by mechanosensitive adhesion complexes at the cell–substrate interface and cell–cell junctions, which respond to but also further transmit physical signals. The mechanosensitivity and mechanotransduction at adhesion complexes are important for regulating tissue cohesiveness and thus are important for collective cell behaviours. Recent studies have shown that the physical properties of the cellular environment, which include matrix stiffness, topography, geometry and the application of external forces, can alter collective cell behaviours, tissue organization and cell-generated forces. On the basis of these findings, we can now start building our understanding of the mechanobiology of collective cell movements that span over multiple length scales from the molecular to the tissue level.

    更新日期:2017-11-08
  • Publisher correction: The essential kinase ATR: ensuring faithful duplication of a challenging genome.
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-08
    Joshua C. Saldivar, David Cortez, Karlene A. Cimprich

    Publisher correction: The essential kinase ATR: ensuring faithful duplication of a challenging genome. Publisher correction: The essential kinase ATR: ensuring faithful duplication of a challenging genome., Published online: 08 November 2017; doi:10.1038/nrm.2017.116

    更新日期:2017-11-08
  • Translation: Immature ribosomes under surveillance
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-08
    Eytan Zlotorynski

    Translation: Immature ribosomes under surveillance Translation: Immature ribosomes under surveillance, Published online: 08 November 2017; doi:10.1038/nrm.2017.117 NatureArticleSnippet(type=short-summary, markup= Ribosome subunits that fail to properly mature enter translation, cause translational stress and become targets of translation surveillance pathways. , isJats=true)

    更新日期:2017-11-08
  • Mechanical forces direct stem cell behaviour in development and regeneration
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-08
    Kyle H. Vining, David J. Mooney

    Stem cells and their local microenvironment, or niche, communicate through mechanical cues to regulate cell fate and cell behaviour and to guide developmental processes. During embryonic development, mechanical forces are involved in patterning and organogenesis. The physical environment of pluripotent stem cells regulates their self-renewal and differentiation. Mechanical and physical cues are also important in adult tissues, where adult stem cells require physical interactions with the extracellular matrix to maintain their potency. In vitro, synthetic models of the stem cell niche can be used to precisely control and manipulate the biophysical and biochemical properties of the stem cell microenvironment and to examine how the mode and magnitude of mechanical cues, such as matrix stiffness or applied forces, direct stem cell differentiation and function. Fundamental insights into the mechanobiology of stem cells also inform the design of artificial niches to support stem cells for regenerative therapies.

    更新日期:2017-11-08
  • Mechanobiology of collective cell behaviours
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-08
    Benoit Ladoux, René-Marc Mège

    The way in which cells coordinate their behaviours during various biological processes, including morphogenesis, cancer progression and tissue remodelling, largely depends on the mechanical properties of the external environment. In contrast to single cells, collective cell behaviours rely on the cellular interactions not only with the surrounding extracellular matrix but also with neighbouring cells. Collective dynamics is not simply the result of many individually moving blocks. Instead, cells coordinate their movements by actively interacting with each other. These mechanisms are governed by mechanosensitive adhesion complexes at the cell–substrate interface and cell–cell junctions, which respond to but also further transmit physical signals. The mechanosensitivity and mechanotransduction at adhesion complexes are important for regulating tissue cohesiveness and thus are important for collective cell behaviours. Recent studies have shown that the physical properties of the cellular environment, which include matrix stiffness, topography, geometry and the application of external forces, can alter collective cell behaviours, tissue organization and cell-generated forces. On the basis of these findings, we can now start building our understanding of the mechanobiology of collective cell movements that span over multiple length scales from the molecular to the tissue level.

    更新日期:2017-11-08
  • Publisher correction: The essential kinase ATR: ensuring faithful duplication of a challenging genome.
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-08
    Joshua C. Saldivar, David Cortez, Karlene A. Cimprich

    Publisher correction: The essential kinase ATR: ensuring faithful duplication of a challenging genome. Publisher correction: The essential kinase ATR: ensuring faithful duplication of a challenging genome., Published online: 08 November 2017; doi:10.1038/nrm.2017.116

    更新日期:2017-11-08
  • Translation: Immature ribosomes under surveillance
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-08
    Eytan Zlotorynski

    Translation: Immature ribosomes under surveillance Translation: Immature ribosomes under surveillance, Published online: 08 November 2017; doi:10.1038/nrm.2017.117 NatureArticleSnippet(type=short-summary, markup= Ribosome subunits that fail to properly mature enter translation, cause translational stress and become targets of translation surveillance pathways. , isJats=true)

    更新日期:2017-11-08
  • Forces as regulators of cell adhesions
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-02
    Christopher S. Chen

    Forces as regulators of cell adhesionsForces as regulators of cell adhesions, Published online: 02 November 2017; doi:10.1038/nrm.2017.112NatureArticleSnippet(type=short-summary, markup=Christopher Chen highlights the early studies of mechanoregulation of cell–matrix adhesions that established mechanobiology as a cross-discplinary research field, isJats=true)

    更新日期:2017-11-02
  • Mechanotransduction: Enforcing protein import
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-02
    Paulina Strzyz

    Mechanotransduction: Enforcing protein importMechanotransduction: Enforcing protein import, Published online: 02 November 2017; doi:10.1038/nrm.2017.114NatureArticleSnippet(type=short-summary, markup=Applying force to the nucleus reduces the diffusion barrier at nuclear pores and promotes nuclear import of certain proteins, including the transcription regulator YAP, depending on their molecular properties., isJats=true)

    更新日期:2017-11-02
  • Mechanobiology by the numbers: a close relationship between biology and physics
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-02
    Ulrich S. Schwarz

    Mechanobiology by the numbers: a close relationship between biology and physicsMechanobiology by the numbers: a close relationship between biology and physics, Published online: 02 November 2017; doi:10.1038/nrm.2017.109NatureArticleSnippet(type=short-summary, markup=Studies of mechanobiology lie at the interface of various scientific disciplines from biology to physics. Ulrich Schwarz discusses the importance of technological advances, quantification and modelling for the progress in understanding the role of forces in biology., isJats=true)

    更新日期:2017-11-02
  • Forces as regulators of cell adhesions
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-02
    Christopher S. Chen

    Forces as regulators of cell adhesionsForces as regulators of cell adhesions, Published online: 02 November 2017; doi:10.1038/nrm.2017.112NatureArticleSnippet(type=short-summary, markup=Christopher Chen highlights the early studies of mechanoregulation of cell–matrix adhesions that established mechanobiology as a cross-discplinary research field, isJats=true)

    更新日期:2017-11-02
  • Mechanotransduction: Enforcing protein import
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-02
    Paulina Strzyz

    Mechanotransduction: Enforcing protein importMechanotransduction: Enforcing protein import, Published online: 02 November 2017; doi:10.1038/nrm.2017.114NatureArticleSnippet(type=short-summary, markup=Applying force to the nucleus reduces the diffusion barrier at nuclear pores and promotes nuclear import of certain proteins, including the transcription regulator YAP, depending on their molecular properties., isJats=true)

    更新日期:2017-11-02
  • Mechanobiology by the numbers: a close relationship between biology and physics
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-02
    Ulrich S. Schwarz

    Studies of mechanobiology lie at the interface of various scientific disciplines from biology to physics. Accordingly, quantification and mathematical modelling have been instrumental in fuelling the progress in this rapidly developing research field, assisting experimental work on many levels.

    更新日期:2017-11-02
  • Transcription: Intragenic enhancers dampen gene expression
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-10-25
    Katharine H. Wrighton

    Transcription: Intragenic enhancers dampen gene expression Nature Reviews Molecular Cell Biology, Published online: 25 October 2017; doi:10.1038/nrm.2017.111 Transcription of enhancer RNA at intragenic enhancers can attenuate the expression of the host gene.

    更新日期:2017-10-30
  • Transcription: Intragenic enhancers dampen gene expression
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-10-25
    Katharine H. Wrighton

    Transcription: Intragenic enhancers dampen gene expression Nature Reviews Molecular Cell Biology, Published online: 25 October 2017; doi:10.1038/nrm.2017.111 Transcription of enhancer RNA at intragenic enhancers can attenuate the expression of the host gene.

    更新日期:2017-10-30
  • Regulation of genome organization and gene expression by nuclear mechanotransduction
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-10-18
    Caroline Uhler, G. V. Shivashankar

    It is well established that cells sense chemical signals from their local microenvironment and transduce them to the nucleus to regulate gene expression programmes. Although a number of experiments have shown that mechanical cues can also modulate gene expression, the underlying mechanisms are far from clear. Nevertheless, we are now beginning to understand how mechanical cues are transduced to the nucleus and how they influence nuclear mechanics, genome organization and transcription. In particular, recent progress in super-resolution imaging, in genome-wide application of RNA sequencing, chromatin immunoprecipitation and chromosome conformation capture and in theoretical modelling of 3D genome organization enables the exploration of the relationship between cell mechanics, 3D chromatin configurations and transcription, thereby shedding new light on how mechanical forces regulate gene expression.

    更新日期:2017-10-30
  • The discovery of catalytic RNA
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-01
    John Abelson

    The discovery of catalytic RNA Nature Reviews Molecular Cell Biology, Published online: 11 October 2017; doi:10.1038/nrm.2017.105 John Abelson recounts the discovery of self-splicing RNA.

    更新日期:2017-10-30
  • Emerging roles of linker histones in regulating chromatin structure and function
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-10-11
    Dmitry V. Fyodorov, Bing-Rui Zhou, Arthur I. Skoultchi, Yawen Bai

    Together with core histones, which make up the nucleosome, the linker histone (H1) is one of the five main histone protein families present in chromatin in eukaryotic cells. H1 binds to the nucleosome to form the next structural unit of metazoan chromatin, the chromatosome, which may help chromatin to fold into higher-order structures. Despite their important roles in regulating the structure and function of chromatin, linker histones have not been studied as extensively as core histones. Nevertheless, substantial progress has been made recently. The first near-atomic resolution crystal structure of a chromatosome core particle and an 11 Å resolution cryo-electron microscopy-derived structure of the 30 nm nucleosome array have been determined, revealing unprecedented details about how linker histones interact with the nucleosome and organize higher-order chromatin structures. Moreover, several new functions of linker histones have been discovered, including their roles in epigenetic regulation and the regulation of DNA replication, DNA repair and genome stability. Studies of the molecular mechanisms of H1 action in these processes suggest a new paradigm for linker histone function beyond its architectural roles in chromatin.

    更新日期:2017-10-30
  • Cell death: BCL-2 proteins feed their own expression
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-01
    Paulina Strzyz

    Cell death: BCL-2 proteins feed their own expression Nature Reviews Molecular Cell Biology, Published online: 11 October 2017; doi:10.1038/nrm.2017.106 Anti-apoptotic BCL-2 proteins can drive their own expression and promote cell survival by regulating Hedgehog signalling transcription activator GLI.

    更新日期:2017-10-30
  • Codon optimality, bias and usage in translation and mRNA decay
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-10-11
    Gavin Hanson, Jeff Coller

    The advent of ribosome profiling and other tools to probe mRNA translation has revealed that codon bias — the uneven use of synonymous codons in the transcriptome — serves as a secondary genetic code: a code that guides the efficiency of protein production, the fidelity of translation and the metabolism of mRNAs. Recent advancements in our understanding of mRNA decay have revealed a tight coupling between ribosome dynamics and the stability of mRNA transcripts; this coupling integrates codon bias into the concept of codon optimality, or the effects that specific codons and tRNA concentrations have on the efficiency and fidelity of the translation machinery. In this Review, we first discuss the evidence for codon-dependent effects on translation, beginning with the basic mechanisms through which translation perturbation can affect translation efficiency, protein folding and transcript stability. We then discuss how codon effects are leveraged by the cell to tailor the proteome to maintain homeostasis, execute specific gene expression programmes of growth or differentiation and optimize the efficiency of protein production.

    更新日期:2017-10-30
  • Piezos thrive under pressure: mechanically activated ion channels in health and disease
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-10-04
    Swetha E. Murthy, Adrienne E. Dubin, Ardem Patapoutian

    Cellular mechanotransduction, the process of translating mechanical forces into biological signals, is crucial for a wide range of physiological processes. A role for ion channels in sensing mechanical forces has been proposed for decades, but their identity in mammals remained largely elusive until the discovery of Piezos. Recent research on Piezos has underscored their importance in somatosensation (touch perception, proprioception and pulmonary respiration), red blood cell volume regulation, vascular physiology and various human genetic disorders.

    更新日期:2017-10-30
  • Transcription: No proper rest in mitosis
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-11-01
    Paulina Strzyz

    Transcription: No proper rest in mitosis Nature Reviews Molecular Cell Biology, Published online: 4 October 2017; doi:10.1038/nrm.2017.102 Low-level transcription persists during mitosis, and the reinstatement of robust gene expression occurs in a stepwise manner, starting with genes regulating cell organization and growth followed by the expression of cell type-specific genes.

    更新日期:2017-10-30
  • Regulation of genome organization and gene expression by nuclear mechanotransduction
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-10-18
    Caroline Uhler, G. V. Shivashankar

    Regulation of genome organization and gene expression by nuclear mechanotransduction Nature Reviews Molecular Cell Biology, Published online: 18 October 2017; doi:10.1038/nrm.2017.101 Mechanical cues from the microenvironment can be efficiently transmitted to the nucleus to engage in the regulation of genome organization and gene expression. Recent technological and theoretical progress sheds new light on the relationships between cell mechanics, nuclear and chromosomal architecture and gene transcription.

    更新日期:2017-10-18
  • Emerging roles of linker histones in regulating chromatin structure and function
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 
    Dmitry V. Fyodorov, Bing-Rui Zhou, Arthur I. Skoultchi, Yawen Bai

    Together with core histones, which make up the nucleosome, the linker histone (H1) is one of the five main histone protein families present in chromatin in eukaryotic cells. H1 binds to the nucleosome to form the next structural unit of metazoan chromatin, the chromatosome, which may help chromatin to fold into higher-order structures. Despite their important roles in regulating the structure and function of chromatin, linker histones have not been studied as extensively as core histones. Nevertheless, substantial progress has been made recently. The first near-atomic resolution crystal structure of a chromatosome core particle and an 11 Å resolution cryo-electron microscopy-derived structure of the 30 nm nucleosome array have been determined, revealing unprecedented details about how linker histones interact with the nucleosome and organize higher-order chromatin structures. Moreover, several new functions of linker histones have been discovered, including their roles in epigenetic regulation and the regulation of DNA replication, DNA repair and genome stability. Studies of the molecular mechanisms of H1 action in these processes suggest a new paradigm for linker histone function beyond its architectural roles in chromatin.

    更新日期:2017-10-11
  • Cell death: BCL-2 proteins feed their own expression
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 
    Paulina Strzyz

    Cell death: BCL-2 proteins feed their own expression Nature Reviews Molecular Cell Biology, Published online: 11 October 2017; doi:10.1038/nrm.2017.106 Anti-apoptotic BCL-2 proteins can drive their own expression and promote cell survival by regulating Hedgehog signalling transcription activator GLI.

    更新日期:2017-10-11
  • Codon optimality, bias and usage in translation and mRNA decay
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 
    Gavin Hanson, Jeff Coller

    The advent of ribosome profiling and other tools to probe mRNA translation has revealed that codon bias — the uneven use of synonymous codons in the transcriptome — serves as a secondary genetic code: a code that guides the efficiency of protein production, the fidelity of translation and the metabolism of mRNAs. Recent advancements in our understanding of mRNA decay have revealed a tight coupling between ribosome dynamics and the stability of mRNA transcripts; this coupling integrates codon bias into the concept of codon optimality, or the effects that specific codons and tRNA concentrations have on the efficiency and fidelity of the translation machinery. In this Review, we first discuss the evidence for codon-dependent effects on translation, beginning with the basic mechanisms through which translation perturbation can affect translation efficiency, protein folding and transcript stability. We then discuss how codon effects are leveraged by the cell to tailor the proteome to maintain homeostasis, execute specific gene expression programmes of growth or differentiation and optimize the efficiency of protein production.

    更新日期:2017-10-11
  • The discovery of catalytic RNA
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 
    John Abelson

    The discovery of catalytic RNA Nature Reviews Molecular Cell Biology, Published online: 11 October 2017; doi:10.1038/nrm.2017.105 John Abelson recounts the discovery of self-splicing RNA.

    更新日期:2017-10-11
  • Transcription: No proper rest in mitosis
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 
    Paulina Strzyz

    Transcription: No proper rest in mitosis Nature Reviews Molecular Cell Biology, Published online: 4 October 2017; doi:10.1038/nrm.2017.102 Low-level transcription persists during mitosis, and the reinstatement of robust gene expression occurs in a stepwise manner, starting with genes regulating cell organization and growth followed by the expression of cell type-specific genes.

    更新日期:2017-10-11
  • Piezos thrive under pressure: mechanically activated ion channels in health and disease
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 
    Swetha E. Murthy, Adrienne E. Dubin, Ardem Patapoutian

    Cellular mechanotransduction, the process of translating mechanical forces into biological signals, is crucial for a wide range of physiological processes. A role for ion channels in sensing mechanical forces has been proposed for decades, but their identity in mammals remained largely elusive until the discovery of Piezos. Recent research on Piezos has underscored their importance in somatosensation (touch perception, proprioception and pulmonary respiration), red blood cell volume regulation, vascular physiology and various human genetic disorders.

    更新日期:2017-10-11
  • Biochemical and cellular properties of insulin receptor signalling
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 
    Rebecca A. Haeusler, Timothy E. McGraw, Domenico Accili

    The mechanism of insulin action is a central theme in biology and medicine. In addition to the rather rare condition of insulin deficiency caused by autoimmune destruction of pancreatic β-cells, genetic and acquired abnormalities of insulin action underlie the far more common conditions of type 2 diabetes, obesity and insulin resistance. The latter predisposes to diseases ranging from hypertension to Alzheimer disease and cancer. Hence, understanding the biochemical and cellular properties of insulin receptor signalling is arguably a priority in biomedical research. In the past decade, major progress has led to the delineation of mechanisms of glucose transport, lipid synthesis, storage and mobilization. In addition to direct effects of insulin on signalling kinases and metabolic enzymes, the discovery of mechanisms of insulin-regulated gene transcription has led to a reassessment of the general principles of insulin action. These advances will accelerate the discovery of new treatment modalities for diabetes.

    更新日期:2017-10-11
  • AMPK: guardian of metabolism and mitochondrial homeostasis
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 
    Sébastien Herzig, Reuben J. Shaw

    Cells constantly adapt their metabolism to meet their energy needs and respond to nutrient availability. Eukaryotes have evolved a very sophisticated system to sense low cellular ATP levels via the serine/threonine kinase AMP-activated protein kinase (AMPK) complex. Under conditions of low energy, AMPK phosphorylates specific enzymes and growth control nodes to increase ATP generation and decrease ATP consumption. In the past decade, the discovery of numerous new AMPK substrates has led to a more complete understanding of the minimal number of steps required to reprogramme cellular metabolism from anabolism to catabolism. This energy switch controls cell growth and several other cellular processes, including lipid and glucose metabolism and autophagy. Recent studies have revealed that one ancestral function of AMPK is to promote mitochondrial health, and multiple newly discovered targets of AMPK are involved in various aspects of mitochondrial homeostasis, including mitophagy. This Review discusses how AMPK functions as a central mediator of the cellular response to energetic stress and mitochondrial insults and coordinates multiple features of autophagy and mitochondrial biology.

    更新日期:2017-10-11
  • In the news: The Lasker goes to Michael Hall
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 
    Kim Baumann

    In the news: The Lasker goes to Michael Hall Nature Reviews Molecular Cell Biology, Published online: 21 September 2017; doi:10.1038/nrm.2017.97 The 2017 Albert Lasker Basic Medical Research Award was awarded to Michael N. Hall (Biozentrum, University of Basel, Switzerland) “for discoveries concerning the nutrient-activated TOR proteins and their central role in the metabolic control of cell growth”.

    更新日期:2017-09-21
  • Ubiquitylation at the crossroads of development and disease
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-20
    Michael Rape

    Human development requires intricate cell specification and communication pathways that allow an embryo to generate and appropriately connect more than 200 different cell types. Key to the successful completion of this differentiation programme is the quantitative and reversible regulation of core signalling networks, and post-translational modification with ubiquitin provides embryos with an essential tool to accomplish this task. Instigated by E3 ligases and reversed by deubiquitylases, ubiquitylation controls many processes that are fundamental for development, such as cell division, fate specification and migration. As aberrant function or regulation of ubiquitylation enzymes is at the roots of developmental disorders, cancer, and neurodegeneration, modulating the activity of ubiquitylation enzymes is likely to provide strategies for therapeutic intervention.

    更新日期:2017-09-21
  • Chromosome biology: Different turfs for cohesin and condensin
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-23
    Eytan Zlotorynski

    In yeast, mitotic chromosome condensation is achieved by cis-chromatin looping, a process in which cohesin and condensin have distinct roles.

    更新日期:2017-09-21
  • Genome editing: CRISPR–Cas becoming more human
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-16
    Kim Baumann

    CRISPR–Cas9 was used in human embryos to correct a dominant heterozygous gene mutation that causes hypertrophic cardiomyopathy.

    更新日期:2017-09-21
  • Cell organization by liquid phase separation
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-06
    Daniel W. Gerlich

    Daniel Gerlich discusses how a study by the Hyman laboratory introduced the theory of liquid phase separation to cell biology and its implications for the understanding of cell organization and function.

    更新日期:2017-09-21
  • Nuclear Envelope: Chromosomes: one BAF layer to bind them all
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-06
    Paulina Strzyz

    Barrier-to-autointegration factor (BAF) forms a layer on the surface of chromatin at late mitosis, guiding the reformation of a single nuclear envelope surrounding all chromosomes.

    更新日期:2017-09-21
  • Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-09
    Nard Kubben, Tom Misteli

    Ageing is the predominant risk factor for many common diseases. Human premature ageing diseases are powerful model systems to identify and characterize cellular mechanisms that underpin physiological ageing. Their study also leads to a better understanding of the causes, drivers and potential therapeutic strategies of common diseases associated with ageing, including neurological disorders, diabetes, cardiovascular diseases and cancer. Using the rare premature ageing disorder Hutchinson–Gilford progeria syndrome as a paradigm, we discuss here the shared mechanisms between premature ageing and ageing-associated diseases, including defects in genetic, epigenetic and metabolic pathways; mitochondrial and protein homeostasis; cell cycle; and stem cell-regenerative capacity.

    更新日期:2017-09-21
  • In the news: The Lasker goes to Michael Hall
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-21
    Kim Baumann

    The 2017 Albert Lasker Basic Medical Research Award was awarded to Michael N. Hall (Biozentrum, University of Basel, Switzerland) “for discoveries concerning the nutrient-activated TOR proteins and their central role in the metabolic control of cell growth”.

    更新日期:2017-09-21
  • Cancer biology: The skin's power of elimination
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-16
    Paulina Strzyz

    The skin is able to counteract tissue aberrancies resulting from tissue overgrowth and to restore normal tissue architecture by eliminating aberrant cells.

    更新日期:2017-09-21
  • The multifaceted roles of PARP1 in DNA repair and chromatin remodelling
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-05
    Arnab Ray Chaudhuri, André Nussenzweig

    Cells are exposed to various endogenous and exogenous insults that induce DNA damage, which, if unrepaired, impairs genome integrity and leads to the development of various diseases, including cancer. Recent evidence has implicated poly(ADP-ribose) polymerase 1 (PARP1) in various DNA repair pathways and in the maintenance of genomic stability. The inhibition of PARP1 is therefore being exploited clinically for the treatment of various cancers, which include DNA repair-deficient ovarian, breast and prostate cancers. Understanding the role of PARP1 in maintaining genome integrity is not only important for the design of novel chemotherapeutic agents, but is also crucial for gaining insights into the mechanisms of chemoresistance in cancer cells. In this Review, we discuss the roles of PARP1 in mediating various aspects of DNA metabolism, such as single-strand break repair, nucleotide excision repair, double-strand break repair and the stabilization of replication forks, and in modulating chromatin structure.

    更新日期:2017-09-21
  • The essential kinase ATR: ensuring faithful duplication of a challenging genome
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-16
    Joshua C. Saldivar, David Cortez, Karlene A. Cimprich

    One way to preserve a rare book is to lock it away from all potential sources of damage. Of course, an inaccessible book is also of little use, and the paper and ink will continue to degrade with age in any case. Like a book, the information stored in our DNA needs to be read, but it is also subject to continuous assault and therefore needs to be protected. In this Review, we examine how the replication stress response that is controlled by the kinase ataxia telangiectasia and Rad3-related (ATR) senses and resolves threats to DNA integrity so that the DNA remains available to read in all of our cells. We discuss the multiple data that have revealed an elegant yet increasingly complex mechanism of ATR activation. This involves a core set of components that recruit ATR to stressed replication forks, stimulate kinase activity and amplify ATR signalling. We focus on the activities of ATR in the control of cell cycle checkpoints, origin firing and replication fork stability, and on how proper regulation of these processes is crucial to ensure faithful duplication of a challenging genome.

    更新日期:2017-09-21
  • Splicing and transcription touch base: co-transcriptional spliceosome assembly and function
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-09
    Lydia Herzel, Diana S. M. Ottoz, Tara Alpert, Karla M. Neugebauer

    Several macromolecular machines collaborate to produce eukaryotic messenger RNA. RNA polymerase II (Pol II) translocates along genes that are up to millions of base pairs in length and generates a flexible RNA copy of the DNA template. This nascent RNA harbours introns that are removed by the spliceosome, which is a megadalton ribonucleoprotein complex that positions the distant ends of the intron into its catalytic centre. Emerging evidence that the catalytic spliceosome is physically close to Pol II in vivo implies that transcription and splicing occur on similar timescales and that the transcription and splicing machineries may be spatially constrained. In this Review, we discuss aspects of spliceosome assembly, transcription elongation and other co-transcriptional events that allow the temporal coordination of co-transcriptional splicing.

    更新日期:2017-09-21
  • Nuclear Envelope: Chromosomes: one BAF layer to bind them all
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-06
    Paulina Strzyz

    Nuclear Envelope: Chromosomes: one BAF layer to bind them all Nature Reviews Molecular Cell Biology, Published online: 6 September 2017; doi:10.1038/nrm.2017.96 Barrier-to-autointegration factor (BAF) forms a layer on the surface of chromatin at late mitosis, guiding the reformation of a single nuclear envelope surrounding all chromosomes.

    更新日期:2017-09-12
  • Fluorescence nanoscopy in cell biology
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-06
    Steffen J. Sahl, Stefan W. Hell, Stefan Jakobs

    Fluorescence nanoscopy uniquely combines minimally invasive optical access to the internal nanoscale structure and dynamics of cells and tissues with molecular detection specificity. While the basic physical principles of 'super-resolution' imaging were discovered in the 1990s, with initial experimental demonstrations following in 2000, the broad application of super-resolution imaging to address cell-biological questions has only more recently emerged. Nanoscopy approaches have begun to facilitate discoveries in cell biology and to add new knowledge. One current direction for method improvement is the ambition to quantitatively account for each molecule under investigation and assess true molecular colocalization patterns via multi-colour analyses. In pursuing this goal, the labelling of individual molecules to enable their visualization has emerged as a central challenge. Extending nanoscale imaging into (sliced) tissue and whole-animal contexts is a further goal. In this Review we describe the successes to date and discuss current obstacles and possibilities for further development.

    更新日期:2017-09-12
  • The emerging complexity of the tRNA world: mammalian tRNAs beyond protein synthesis
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-06
    Paul Schimmel

    The discovery of the genetic code and tRNAs as decoders of the code transformed life science. However, after establishing the role of tRNAs in protein synthesis, the field moved to other parts of the RNA world. Now, tRNA research is blooming again, with demonstration of the involvement of tRNAs in various other pathways beyond translation and in adapting translation to environmental cues. These roles are linked to the presence of tRNA sequence variants known as isoacceptors and isodecoders, various tRNA base modifications, the versatility of protein binding partners and tRNA fragmentation events, all of which collectively create an incalculable complexity. This complexity provides a vast repertoire of tRNA species that can serve various functions in cellular homeostasis and in adaptation of cellular functions to changing environments, and it likely arose from the fundamental role of RNAs in early evolution.

    更新日期:2017-09-12
  • Cell organization by liquid phase separation
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-09-06
    Daniel W. Gerlich

    Cell organization by liquid phase separation Nature Reviews Molecular Cell Biology, Published online: 6 September 2017; doi:10.1038/nrm.2017.93 Daniel Gerlich discusses how a study by the Hyman laboratory introduced the theory of liquid phase separation to cell biology and its implications for the understanding of cell organization and function.

    更新日期:2017-09-12
  • Cytosolic lipolysis and lipophagy: two sides of the same coin
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-30
    Rudolf Zechner, Frank Madeo, Dagmar Kratky

    Fatty acids are the most efficient substrates for energy production in vertebrates and are essential components of the lipids that form biological membranes. Synthesis of triacylglycerols from non-esterified free fatty acids (FFAs) combined with triacylglycerol storage represents a highly efficient strategy to stockpile FFAs in cells and prevent FFA-induced lipotoxicity. Although essentially all vertebrate cells have some capacity to store and utilize triacylglycerols, white adipose tissue is by far the largest triacylglycerol depot and is uniquely able to supply FFAs to other tissues. The release of FFAs from triacylglycerols requires their enzymatic hydrolysis by a process called lipolysis. Recent discoveries thoroughly altered and extended our understanding of lipolysis. This Review discusses how cytosolic 'neutral' lipolysis and lipophagy, which utilizes 'acid' lipolysis in lysosomes, degrade cellular triacylglycerols as well as how these pathways communicate, how they affect lipid metabolism and energy homeostasis and how their dysfunction affects the pathogenesis of metabolic diseases. Answers to these questions will likely uncover novel strategies for the treatment of prevalent metabolic diseases.

    更新日期:2017-09-12
  • Regulation of heat shock transcription factors and their roles in physiology and disease
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-30
    Rocio Gomez-Pastor, Eileen T. Burchfiel, Dennis J. Thiele

    The heat shock transcription factors (HSFs) were discovered over 30 years ago as direct transcriptional activators of genes regulated by thermal stress, encoding heat shock proteins. The accepted paradigm posited that HSFs exclusively activate the expression of protein chaperones in response to conditions that cause protein misfolding by recognizing a simple promoter binding site referred to as a heat shock element. However, we now realize that the mammalian family of HSFs comprises proteins that independently or in concert drive combinatorial gene regulation events that activate or repress transcription in different contexts. Advances in our understanding of HSF structure, post-translational modifications and the breadth of HSF-regulated target genes have revealed exciting new mechanisms that modulate HSFs and shed new light on their roles in physiology and pathology. For example, the ability of HSF1 to protect cells from proteotoxicity and cell death is impaired in neurodegenerative diseases but can be exploited by cancer cells to support their growth, survival and metastasis. These new insights into HSF structure, function and regulation should facilitate the development tof new disease therapeutics to manipulate this transcription factor family.

    更新日期:2017-09-12
  • Genome organization: A vision of 3D chromatin organization
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 
    Kim Baumann

    Genome organization: A vision of 3D chromatin organization Nature Reviews Molecular Cell Biology, Published online: 23 August 2017; doi:10.1038/nrm.2017.88 A new imaging technique (ChromEMT) enables the visualization of the local polymer structure and global 3D organization of chromatin in the nucleus of intact interphase and mitotic human cells.

    更新日期:2017-09-12
  • Chromosome biology: Different turfs for cohesin and condensin
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-23
    Eytan Zlotorynski

    Chromosome biology: Different turfs for cohesin and condensin Nature Reviews Molecular Cell Biology, Published online: 23 August 2017; doi:10.1038/nrm.2017.90 In yeast, mitotic chromosome condensation is achieved by cis-chromatin looping, a process in which cohesin and condensin have distinct roles.

    更新日期:2017-09-12
  • Cancer biology: The skin's power of elimination
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-16
    Paulina Strzyz

    The skin is able to counteract tissue aberrancies resulting from tissue overgrowth and to restore normal tissue architecture by eliminating aberrant cells.

    更新日期:2017-09-06
  • Genome editing: CRISPR–Cas becoming more human
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-16
    Kim Baumann

    CRISPR–Cas9 was used in human embryos to correct a dominant heterozygous gene mutation that causes hypertrophic cardiomyopathy.

    更新日期:2017-09-06
  • The multifaceted roles of PARP1 in DNA repair and chromatin remodelling
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-07-05
    Arnab Ray Chaudhuri, André Nussenzweig

    Cells are exposed to various endogenous and exogenous insults that induce DNA damage, which, if unrepaired, impairs genome integrity and leads to the development of various diseases, including cancer. Recent evidence has implicated poly(ADP-ribose) polymerase 1 (PARP1) in various DNA repair pathways and in the maintenance of genomic stability. The inhibition of PARP1 is therefore being exploited clinically for the treatment of various cancers, which include DNA repair-deficient ovarian, breast and prostate cancers. Understanding the role of PARP1 in maintaining genome integrity is not only important for the design of novel chemotherapeutic agents, but is also crucial for gaining insights into the mechanisms of chemoresistance in cancer cells. In this Review, we discuss the roles of PARP1 in mediating various aspects of DNA metabolism, such as single-strand break repair, nucleotide excision repair, double-strand break repair and the stabilization of replication forks, and in modulating chromatin structure.

    更新日期:2017-09-06
  • Splicing and transcription touch base: co-transcriptional spliceosome assembly and function
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-09
    Lydia Herzel, Diana S. M. Ottoz, Tara Alpert, Karla M. Neugebauer

    Several macromolecular machines collaborate to produce eukaryotic messenger RNA. RNA polymerase II (Pol II) translocates along genes that are up to millions of base pairs in length and generates a flexible RNA copy of the DNA template. This nascent RNA harbours introns that are removed by the spliceosome, which is a megadalton ribonucleoprotein complex that positions the distant ends of the intron into its catalytic centre. Emerging evidence that the catalytic spliceosome is physically close to Pol II in vivo implies that transcription and splicing occur on similar timescales and that the transcription and splicing machineries may be spatially constrained. In this Review, we discuss aspects of spliceosome assembly, transcription elongation and other co-transcriptional events that allow the temporal coordination of co-transcriptional splicing.

    更新日期:2017-09-06
  • Mitochondrial diseases: the contribution of organelle stress responses to pathology
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-09
    Anu Suomalainen, Brendan J. Battersby

    Mitochondrial diseases affect one in 2,000 individuals; they can present at any age and they can manifest in any organ. How defects in mitochondria can cause such a diverse range of human diseases remains poorly understood. Insight into this diversity is emerging from recent research that investigated defects in mitochondrial protein synthesis and mitochondrial DNA maintenance, which showed that many cell-specific stress responses are induced in response to mitochondrial dysfunction. Studying the molecular regulation of these stress responses might increase our understanding of the pathogenesis and variability of human mitochondrial diseases.

    更新日期:2017-09-06
  • The essential kinase ATR: ensuring faithful duplication of a challenging genome
    Nat. Rev. Mol. Cell Biol. (IF 46.602) Pub Date : 2017-08-16
    Joshua C. Saldivar, David Cortez, Karlene A. Cimprich

    One way to preserve a rare book is to lock it away from all potential sources of damage. Of course, an inaccessible book is also of little use, and the paper and ink will continue to degrade with age in any case. Like a book, the information stored in our DNA needs to be read, but it is also subject to continuous assault and therefore needs to be protected. In this Review, we examine how the replication stress response that is controlled by the kinase ataxia telangiectasia and Rad3-related (ATR) senses and resolves threats to DNA integrity so that the DNA remains available to read in all of our cells. We discuss the multiple data that have revealed an elegant yet increasingly complex mechanism of ATR activation. This involves a core set of components that recruit ATR to stressed replication forks, stimulate kinase activity and amplify ATR signalling. We focus on the activities of ATR in the control of cell cycle checkpoints, origin firing and replication fork stability, and on how proper regulation of these processes is crucial to ensure faithful duplication of a challenging genome.

    更新日期:2017-09-06
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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