Review Articles

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  • Integrator is the only metazoan-specific RNA polymerase II (Pol II)-associated large multisubunit complex. Processing of non-coding RNAs by Integrator is essential for their biogenesis, and, at protein-coding genes, Integrator regulates Pol II promoter-proximal pausing and elongation. Consequently, Integrator has diverse roles in development and tumorigenesis.

    • Sarah A. Welsh
    • Alessandro Gardini
    Review Article
  • Cell competition results in stochastic cell turnover or elimination of less fit cells from a tissue. Although cell competition generally supports tissue development and homeostasis, it can also promote malignant growth and is subverted during ageing. Addressing how cell fitness is determined and sensed is being actively pursued.

    • Sanne M. van Neerven
    • Louis Vermeulen
    Review Article
  • Cell–extracellular matrix (ECM) interactions occur at specialized, multi-protein adhesion complexes, with clustered integrins as the predominant ECM receptors. Progress in characterization of adhesion composition, organization and dynamics in response to force has improved understanding of adhesion maturation and turnover and the relationships between adhesion structures and functions.

    • Pakorn Kanchanawong
    • David A. Calderwood
    Review Article
  • PIWI-interacting RNAs (piRNAs) are small non-coding RNAs with essential roles in germ line development through silencing of transposable elements and in regulation of protein-coding genes. Recent studies have deepened our understanding of the biogenesis and function of piRNAs and their roles in infertility, cancer and neurological diseases in humans.

    • Xin Wang
    • Anne Ramat
    • Mo-Fang Liu
    Review Article
  • Podosomes and invadopodia, collectively called ‘invadosomes’, are actin-based structures that drive proteolytic invasion in various physiologically relevant cell types (including osteoclasts, immune cells, endothelial cells and fibroblasts) and in cancer cells. Recent work has expanded our understanding of the architecture and mechanisms of invadosomes, and has revealed their diverse functions beyond matrix degradation.

    • Stefan Linder
    • Pasquale Cervero
    • John Condeelis
    Review Article
  • Microautophagy involves direct engulfment of cytoplasmic components, including proteins and organelles, by lysosomes and late endosomes for degradation. Although it is one of three main types of autophagy — along with macroautophagy and chaperone-mediated autophagy — its mechanisms and physiological roles have only recently begun to emerge.

    • Liming Wang
    • Daniel J. Klionsky
    • Han-Ming Shen
    Review Article
  • Fidelity of meiosis in human oocytes can be compromised, leading to egg aneuploidy and impaired embryo development, which increase with advanced maternal age. Recent studies have shed light on the molecular mechanisms underlying aberrant chromosome segregation during oocyte meiosis and the impact of ageing on this process.

    • Chloe Charalambous
    • Alexandre Webster
    • Melina Schuh
    Review Article
  • Transmembrane proteins associate with specific subsets of lipids, which create nano-environments with unique properties. Better understanding of how these nano-environments regulate protein dynamics and function will afford means to control activities of transmembrane proteins, many of which serve essential signalling and transport roles.

    • Ilya Levental
    • Ed Lyman
    Review Article
  • During mammalian development, certain regulatory-gene promoters acquire both histone modifications associated with gene activation and with gene repression (bivalent chromatin), which is key to cell-lineage specification. Recent work has expanded our understanding of the molecular basis of bivalent chromatin and its roles in development and cancer.

    • Trisha A. Macrae
    • Julie Fothergill-Robinson
    • Miguel Ramalho-Santos
    Review Article
  • Actin cytoskeleton underlies key cellular processes, such as membrane dynamics and cell migration. Despite years of research, how cells regulate actin filament assembly and disassembly to establish dynamic actin structures that fulfil these functions remains an exciting area of study.

    • Pekka Lappalainen
    • Tommi Kotila
    • Guillaume Romet-Lemonne
    Review Article
  • The generation of membrane curvature is essential for the formation of membrane tubules, sheets and vesicles, and hence, underlies membrane trafficking events. Various protein-based mechanisms function in membrane bending, and these appear to be organized in time and space by protein coats, including clathrin, caveolar coat complex, and COPI and COPII coats.

    • Michael M. Kozlov
    • Justin W. Taraska
    Review Article
  • Stem cell function declines during ageing, resulting in the loss of tissue integrity and health deterioration. Ageing is associated with defects in the maintenance of stem cell quiescence and cell differentiation ability, clonal expansion and infiltration of immune cells in the niche. This Review discusses the mechanisms underlying ageing in stem cells and their niches, and potential rejuvenation strategies.

    • Anne Brunet
    • Margaret A. Goodell
    • Thomas A. Rando
    Review Article
  • Mitochondrial respiratory function needs to adapt to the energetic demands of the cell. These adaptive responses encompass transcriptional, translational and post-translational mechanisms that together enable regulation of respiratory chain assembly and mitochondrial membrane remodelling to fine-tune energy generation in accordance with intracellular and extracellular cues.

    • Christopher F. Bennett
    • Pedro Latorre-Muro
    • Pere Puigserver
    Review Article
  • Alternative cleavage and polyadenylation (APA) generates mRNA isoforms with alternative 3′ untranslated regions; these isoforms modulate protein abundance and functionality, including through subcellular localization of mRNA and translation. APA is modulated by signalling pathways that control co-transcriptional and post-transcriptional processes, and its dysregulation affects cell responses to environmental changes.

    • Sibylle Mitschka
    • Christine Mayr
    Review Article
  • Reactive oxygen species (ROS) signalling is crucial in plant responses to abiotic and biotic stresses. This Review discusses our current understanding of ROS regulation and sensing in plants, key regulatory hubs that connect ROS signalling with other stress-response pathways and how ROS signalling could be harnessed to increase plant resilience to environmental stress.

    • Ron Mittler
    • Sara I. Zandalinas
    • Frank Van Breusegem
    Review Article
  • Sumoylation regulates thousands of proteins, many of which are nuclear. Recent studies have implicated sumoylation in liquid–liquid phase separation and assembly of nuclear bodies, and have uncovered its roles in immunity and pluripotency and links to disease, thereby opening new therapeutic avenues.

    • Alfred C. O. Vertegaal
    Review Article
  • The Mediator complex is an important regulator of RNA polymerase II. This Review discusses recent structural insights into Mediator function and proposes a model that reconciles contradictory data on whether enhancer–promoter communication during transcription is direct or indirect.

    • William F. Richter
    • Shraddha Nayak
    • Dylan J. Taatjes
    Review Article
  • RNA silencing through small RNAs is a major antiviral immunity system in plants. Recent findings are uncovering the roles of RNA silencing in immunity against non-viral pathogens, which is mediated by trans-kingdom RNA movements in vesicles or as extracellular nucleoproteins. RNA silencing also enables the crosstalk between other plant immunity systems.

    • Sara Lopez-Gomollon
    • David C. Baulcombe
    Review Article
  • Homeostasis and function of neurons rely on long-distance, bidirectional microtubule-based transport along the axon, which is driven by both dynein and kinesin motors. How these motors are regulated by a plethora of adaptors and effectors to ensure appropriate and robust distribution of cargos is an area of intense study.

    • Sydney E. Cason
    • Erika L. F. Holzbaur
    Review Article
  • Phosphoinositides are signalling, membrane lipids derived from phosphatidylinositol, whose intracellular distribution and interconversion via phosphoinositide kinases and phosphatases is tightly coupled to membrane dynamics. Accordingly, phosphoinositides are now recognized as key regulators of endocytic and exocytic traffic, the autolysosomal system, and membrane contact site organization and function.

    • York Posor
    • Wonyul Jang
    • Volker Haucke
    Review Article