Latest Reviews

  • Review Article |

    The aggregation of proteins into amyloid fibrils and their deposition into plaques and intracellular inclusions is the hallmark of amyloid disease. Recent advances in structural biology techniques have provided insight into how amyloid structure may affect the ability of fibrils to spread in a prion-like manner and into their roles in disease.

    • Matthew G. Iadanza
    • , Matthew P. Jackson
    • , Eric W. Hewitt
    • , Neil A. Ranson
    •  & Sheena E. Radford
  • Review Article |

    The cleavage of microRNA (miRNA) precursors by Drosha and Dicer and their loading with Argonaute proteins into RNA-induced silencing complexes are key steps in miRNA biogenesis. Recent studies have clarified the mechanisms of action of these molecular machines and discovered non-canonical miRNA biogenesis pathways.

    • Thomas Treiber
    • , Nora Treiber
    •  & Gunter Meister
  • Review Article |

    Endocytosed membrane proteins can either be degraded in the lysosome or recycled back to the membrane. This decision, which has an impact on protein levels, spatial distribution and function, is controlled by recycling machineries at the endosome that recognize and segregate cargo destined for recycling, thereby preventing its degradation.

    • Peter J. Cullen
    •  & Florian Steinberg
  • Review Article |

    Uptake of Ca2+ ions by mitochondria regulates their functions and serves to buffer Ca2+ concentrations to maintain cellular Ca2+ homeostasis. Better understanding of the mechanisms, regulation and (patho)physiology of mitochondrial Ca2+ influx and efflux offers the possibility to target mitochondrial Ca2+ machineries for therapeutic benefit.

    • Carlotta Giorgi
    • , Saverio Marchi
    •  & Paolo Pinton
  • Review Article |

    MicroRNAs (miRNAs) are key regulators of biological processes. Recent discoveries have expanded our understanding of the control of miRNA function in animals, through alternative processing, miRNA-sequence editing, post-translational modifications of Argonaute proteins, subcellular localization and regulation of miRNA–target interactions.

    • Luca F. R. Gebert
    •  & Ian J. MacRae
  • Review Article |

    G protein-coupled receptors (GPCRs) control a plethora of signalling pathways in various contexts. Importantly, a single GPCR can elicit different responses depending on the bound ligand — a phenomenon known as biased agonism. Increasing molecular and structural understanding of biased agonism offers the possibility of designing improved GPCR-targeting drugs.

    • Denise Wootten
    • , Arthur Christopoulos
    • , Maria Marti-Solano
    • , M. Madan Babu
    •  & Patrick M. Sexton
  • Review Article |

    Metabolomics and lipidomics have enabled the identification of metabolites (such as lipids, amino acids and bile acids) and metabolic pathways that modulate insulin sensitivity both directly and indirectly. Understanding the metabolic adaptations involved in insulin resistance may lead to novel approaches for preventing and treating T2DM.

    • Qin Yang
    • , Archana Vijayakumar
    •  & Barbara B. Kahn
  • Review Article |

    Protein degradation by the proteasome is crucial for the control of many cellular processes, and defects in proteasomal degradation may lead to cancer and neurodegeneration. TOR complex 1 has a key role in regulating proteasome abundance and assembly and in integrating proteasomal activity with autophagy pathways and, more generally, cell physiology.

    • Adrien Rousseau
    •  & Anne Bertolotti
  • Review Article |

    Translation deregulation causes many human diseases, which can be broadly categorized into tRNA or ribosomal dysfunction, and deregulation of the integrated stress response or the mTOR pathway. The complexity of the translation process and its cellular contexts could explain the phenotypic variability of these disorders.

    • Soroush Tahmasebi
    • , Arkady Khoutorsky
    • , Michael B. Mathews
    •  & Nahum Sonenberg
  • Review Article |

    Recent studies in model organisms uncovered prominent links between autophagy and ageing, suggesting that by removing superfluous or damaged cellular content through lysosomal degradation, autophagy supports tissue and organismal fitness and promotes longevity. Thus, autophagy induction could be considered a strategy to extend lifespan.

    • Malene Hansen
    • , David C. Rubinsztein
    •  & David W. Walker
  • Review Article |

    Core promoters of RNA polymerase II enable highly regulated transcription initiation by integrating cues from distal enhancers. The emerging diversity of core promoters defines distinct transcription programmes and can explain the nature and outcome of transcription initiation at gene start sites and at enhancers.

    • Vanja Haberle
    •  & Alexander Stark
  • Review Article |

    Metabolism feeds into gene regulation, allowing adaptation of gene expression to satisfy cellular needs, including in pathological scenarios such as cancer. Metabolism modulates gene expression through metabolites, which serve as cofactors for DNA and histone modifiers, and through metabolic enzymes, which locally regulate chromatin and transcription in the nucleus.

    • Xinjian Li
    • , Gabor Egervari
    • , Yugang Wang
    • , Shelley L. Berger
    •  & Zhimin Lu
  • Review Article |

    Decline in stem cell function causes loss of tissue homeostasis and increased incidence of age-related diseases. During ageing, adult stem cells accumulate damage and the niche in which they reside malfunctions. These defects are associated with changes in the epigenome that contribute to organ dysfunction and disease.

    • Maria Ermolaeva
    • , Francesco Neri
    • , Alessandro Ori
    •  & K. Lenhard Rudolph
  • Review Article |

    Taking advantage of genetic engineering, synthetic biology allows control and design of new cell functions. Recent advances in the development of genetic tools and the assembly of progressively more sophisticated gene circuits have made ‘designer cells’ a reality, with applications ranging from industry and biotechnology to medicine.

    • Mingqi Xie
    •  & Martin Fussenegger
  • Review Article |

    The tumour suppressor PTEN regulates various cellular processes, including maintenance of genomic stability, cell survival, migration, proliferation and metabolism. Recent studies into the regulation of PTEN levels and activity provide new insights into its anti-oncogenic functions and offer novel opportunities for cancer treatment.

    • Yu-Ru Lee
    • , Ming Chen
    •  & Pier Paolo Pandolfi
  • Review Article |

    DNA methylation in plants mediates gene expression, transposon silencing, chromosome interactions and genome stability. It is therefore not surprising that the regulation of DNA methylation is important for plant development and for plant responses to biotic and abiotic stresses.

    • Huiming Zhang
    • , Zhaobo Lang
    •  & Jian-Kang Zhu
  • Review Article |

    Ribosomes encounter obstacles during translation elongation that cause their stalling and can have a profound impact on protein yield. Ribosome stalling depends on the genetic code, amino acid availability, regulatory elements and mRNA context and can be resolved by resumption of translation or by ribosome rescue and recycling.

    • Anthony P. Schuller
    •  & Rachel Green
  • Review Article |

    Transcription elongation by RNA polymerase II (Pol II) involves pausing of Pol II at promoter-proximal regions. Pol II release into gene bodies (productive elongation) is controlled by many transcription-specific factors, enhancers and factors that are canonically associated with genome maintenance.

    • Fei Xavier Chen
    • , Edwin R. Smith
    •  & Ali Shilatifard
  • Review Article |

    The maternal-to-zygotic transition (MZT) is defined as the transition from maternal gene expression in the oocyte to zygotic genome activation and embryonic-driven development. Recent studies have improved our understanding of the dynamics of the MZT, which is characterized by global DNA demethylation, chromatin remodelling, genome reorganization and substantial transcriptional changes.

    • Melanie A. Eckersley-Maslin
    • , Celia Alda-Catalinas
    •  & Wolf Reik
  • Review Article |

    Microtubules are highly dynamic tubulin polymers, and their dynamics are associated with a conformational cycle of individual tubulin subunits in the lattice. Recent evidence suggests that fine-tuning microtubule dynamics is enabled by the allosteric coupling of tubulin subunits, which propagates conformational changes through the lattice.

    • Gary J. Brouhard
    •  & Luke M. Rice
  • Review Article |

    Single-cell technologies are transforming our understanding of pre-implantation and early post-implantation development and of in vitro pluripotency. Specifically, single-cell transcriptomics and imaging and the accompanying bioinformatics methods have enabled precision interrogation of cell fate choices and cell lineage diversification, which occur at the level of the individual cell.

    • Blanca Pijuan-Sala
    • , Carolina Guibentif
    •  & Berthold Göttgens
  • Review Article |

    Cytoplasmic dynein is a minus-end-directed microtubule-based motor that transports a wide range of cargoes, including organelles, RNAs, protein complexes and viruses. How a single motor can interact with and traffic such different cargoes has been unclear. Recent studies indicate how adaptor proteins, which can both activate dynein and link it to cargo, play an important role in this process.

    • Samara L. Reck-Peterson
    • , William B. Redwine
    • , Ronald D. Vale
    •  & Andrew P. Carter
  • Review Article |

    Transforming growth factor-β (TGFβ) family cytokines are important regulators of cell fate with pleiotropic roles in development, tissue homeostasis, regeneration and tumorigenesis. Recent studies revealed that this context dependency relies on the convergence between TGFβ signals and other contextual inputs, whereby transcription factors downstream of these pathways collaboratively act to regulate gene expression.

    • Charles J. David
    •  & Joan Massagué
  • Review Article |

    The selective degradation of cellular components via chaperone-mediated autophagy (CMA) functions to regulate a wide range of cellular processes, from metabolism to DNA repair and cellular reprogramming. Recent in vivo studies have enabled to dissect key roles of CMA in ageing and ageing-associated disorders such as cancer and neurodegeneration.

    • Susmita Kaushik
    •  & Ana Maria Cuervo
  • Review Article |

    Autophagy is a process of cellular self-consumption that promotes cell survival in response to stress. Various human pathologies, including cancer, neurodegeneration and inflammation, have been associated with aberrant autophagy, and recent studies of the mechanisms and regulation of autophagy in higher eukaryotes have suggested new therapeutic possibilities.

    • Ivan Dikic
    •  & Zvulun Elazar
  • Review Article |

    Clathrin-mediated endocytosis is the main mechanism for internalization of cell-surface molecules and surface-bound cargoes. Although the machineries that drive the formation of endocytic vesicle are intricate, an understanding of endocytosis is being unravelled at the molecular level.

    • Marko Kaksonen
    •  & Aurélien Roux
  • Review Article |

    Membrane lipids exhibit a remarkable diversity — they vary in structure and chemical properties, and their distribution between different membranes and their subcompartments is highly heterogeneous. Recent progress in studies of membrane lipids has broadened our understanding of how this diversity affects membrane properties and membrane-associated processes.

    • Takeshi Harayama
    •  & Howard Riezman
  • Review Article |

    Most eukaryotic cells contain a single centrosome with a pair of centrioles, which duplicate before mitosis. Defects in duplication lead to aberrant numbers of centrioles and centrosomes. Recent insights into mechanisms of centriole biogenesis and centriole number control are helping us to better understand the links between aberrant centrosome number and human disease.

    • Erich A. Nigg
    •  & Andrew J. Holland
  • Review Article |

    Recent studies that combine cell biology, structural and proteomic approaches have unravelled how ubiquitin is conjugated to damaged mitochondria through the PINK1–parkin pathway to promote mitophagy. The findings have revealed links between PINK1–parkin, antigen presentation and neuronal survival and have implications for the understanding of neurological disorders.

    • J. Wade Harper
    • , Alban Ordureau
    •  & Jin-Mi Heo
  • Review Article |

    Recent proteome-wide studies have uncovered hundreds of RNA-binding proteins (RBPs) that lack conventional RNA-binding domains. These RBPs instead use intrinsically disordered regions, protein–protein interaction interfaces and enzymatic cores to bind RNA. Interestingly, some RBPs are regulated by RNA rather than regulate RNA.

    • Matthias W. Hentze
    • , Alfredo Castello
    • , Thomas Schwarzl
    •  & Thomas Preiss
  • Review Article |

    Cells produce a wide variety of extracellular vesicles (subdivided into exosomes and microvesicles), which carry a multitude of cargoes, including proteins, lipids and nucleic acids. These vesicles have emerged as important means of cell–cell communication in physiology and disease, and their use in the clinic is now being explored.

    • Guillaume van Niel
    • , Gisela D'Angelo
    •  & Graça Raposo
  • Review Article |

    The assembly and maintenance of heterochromatin are carried out by distinct mechanisms that include factors that bind nascent transcripts to recruit chromatin-modifying enzymes. The resulting post-translational modifications on heterochromatic histones contribute to the regulation of development by restricting lineage-specific gene expression.

    • Robin C. Allshire
    •  & Hiten D. Madhani
  • Review Article |

    The evolutionarily conserved mediator of RNA polymerase II transcription (Mediator) complex is a general regulator of transcription. Recent structural and functional studies have provided important insights into the mechanisms of transcription activation by Mediator and have also revealed a new function of this complex in genome organization and suggested that it could be therapeutically targeted in disease.

    • Julie Soutourina
  • Review Article |

    Gene expression programmes that are induced by inflammatory or oncogenic signals are controlled by shared chromatin regulators. Such chromatin dependencies are known to regulate oncogenes and inflammation-promoting genes and can be leveraged to combine and increase the effectiveness of immune-cell-based therapies with epigenetic therapies.

    • Ivan Marazzi
    • , Benjamin D. Greenbaum
    • , Diana H. P. Low
    •  & Ernesto Guccione
  • Review Article |

    Cells activate a transcriptional response known as the mitochondrial unfolded protein response (UPRmt) when mitochondrial integrity and function are impaired to promote their recovery. Recent insights into the regulation, mechanisms and functions of the UPRmt have uncovered important links to ageing and ageing-associated diseases.

    • Tomer Shpilka
    •  & Cole M. Haynes
  • Review Article |

    Structures in 5′ untranslated regions of eukaryotic mRNAs contribute to gene regulation by controlling cap-dependent and cap-independent translation initiation through diverse mechanisms. New structure probing technologies coupled with techniques such as compensatory mutagenesis will likely identify new structured RNA elements and help elucidate their function.

    • Kathrin Leppek
    • , Rhiju Das
    •  & Maria Barna
  • Review Article |

    Sphingolipids are a major class of lipids, comprising various species with diverse functions. In addition to being structural elements of membranes, many sphingolipids are bioactive and regulate a myriad of cellular processes. Recent advances have shed new light on the complexity of sphingolipid metabolism and their various roles in physiology and disease.

    • Yusuf A. Hannun
    •  & Lina M. Obeid
  • Review Article |

    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.

    • Julia D. Ransohoff
    • , Yuning Wei
    •  & Paul A. Khavari
  • Review Article |

    Coordinated movements of cell collectives are important for morphogenesis, tissue regeneration and cancer cell dissemination. Recent studies, mainly using novel in vitro approaches, have provided new insights into the mechanisms governing this multicellular coordination, highlighting the key role of the mechanosensitivity of adherens junctions and mechanical cell–cell coupling in collective cell behaviours.

    • Benoit Ladoux
    •  & René-Marc Mège
  • Review Article |

    Physical cues regulate stem cell fate and function during embryonic development and in adult tissues. The biophysical and biochemical properties of the stem cell microenvironment can be precisely manipulated using synthetic niches, which provide key insights into how mechanical stimuli regulate stem cell function and can be used to maintain and guide stem cells for regenerative therapies.

    • Kyle H. Vining
    •  & David J. Mooney
  • Review Article |

    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.

    • Caroline Uhler
    •  & G. V. Shivashankar
  • Review Article |

    The uneven use of the synonymous amino acid codons in the transcriptome coupled with the relative concentrations of different tRNA species gives rise to non-uniform codon decoding rates by ribosomes, known as codon optimality. Codon optimality influences translation efficiency and fidelity, protein folding and mRNA decay.

    • Gavin Hanson
    •  & Jeff Coller
  • Review Article |

    Linker histones bind to nucleosomes and have been traditionally perceived as structural units of chromatin. Recent advances indicate that these histones have an active role in the control of chromatin architecture and function, participating in the regulation of gene expression, DNA replication and DNA repair.

    • Dmitry V. Fyodorov
    • , Bing-Rui Zhou
    • , Arthur I. Skoultchi
    •  & Yawen Bai
  • Review Article |

    Research over the past few decades has elucidated the biochemical mechanisms underlying insulin receptor signalling. Recent insights into the complexity of its temporal and tissue-specific regulation, which involves various combinations of signalling modules in different cell types, are shedding light on the pleiotropic effects of insulin action and the pathogenesis of insulin resistance.

    • Rebecca A. Haeusler
    • , Timothy E. McGraw
    •  & Domenico Accili