Reviews & Analysis

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  • Human organoids are valuable models for the study of development and disease and for drug discovery, thus complementing traditional animal models. The generation of organoids from patient biopsy samples has enabled researchers to study, for example, infectious diseases, genetic disorders and cancers. This Review discusses the advantages, disadvantages and future challenges of the use of organoids as models for human biology.

    • Jihoon Kim
    • Bon-Kyoung Koo
    • Juergen A. Knoblich
    Review Article
  • Recent studies have highlighted the contribution of RNA to cellular liquid–liquid phase separation and condensate formation. RNA features modulate the composition and biophysical properties of RNA–protein condensates, which have various cellular functions, including RNA transport and localization, supporting catalytic processes and responding to stress.

    • Christine Roden
    • Amy S. Gladfelter
    Review Article
  • Different obstacles can stall the progression of replication forks. Recent studies have revealed that stalled forks are remarkably diverse in their composition and architecture. This plasticity enables fork remodelling, processing and restart in response to specific types of replication stress, thereby influencing tumorigenesis and innate immunity.

    • Matteo Berti
    • David Cortez
    • Massimo Lopes
    Review Article
  • Extracellular signal-regulated kinase 1 (ERK1) and ERK2 relay cell growth and mitogenic signals to multiple substrates, and thus control essential physiological processes. This Review discusses the regulation of ERKs, and their control of cell proliferation, cell survival, cell growth, cell metabolism, cell migration and cell differentiation.

    • Hugo Lavoie
    • Jessica Gagnon
    • Marc Therrien
    Review Article
  • The non-canonical addition of non-templated nucleotides to RNA 3′ ends (tailing) by terminal nucleotidyltransferases includes uridylation, mixed-nucleotide tailing and post-transcriptional polyadenylation. Recent studies of human terminal nucleotidyltransferases have revealed their distinct specificities for substrates, including mRNAs, microRNAs and other non-coding RNAs, and how they control RNA stability and activity.

    • Sha Yu
    • V. Narry Kim
    Review Article
  • Extracellular vesicles transfer a variety of cellular components between cells — including proteins, lipids and nucleic acids. There is now evidence indicating that these cargoes, in particular RNAs, can affect the function of recipient cells. Extracellular vesicles are now being actively tested as biomarkers and delivery vehicles for therapeutic agents.

    • Killian O’Brien
    • Koen Breyne
    • Xandra O. Breakefield
    Review Article
  • The unfolded protein response (UPR) comprises a network of signalling pathways that reprogramme transcription, translation and protein modifications to relieve the load of unfolded or misfolded proteins in the endoplasmic reticulum lumen and restore proteostasis. Understanding the regulation of the UPR and the role it has in the pathophysiology of various cell types and organs might open new therapeutic avenues.

    • Claudio Hetz
    • Kezhong Zhang
    • Randal J. Kaufman
    Review Article
  • The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway senses DNA in the cytoplasm, whether of pathogenic or endogenous (chromatin or mitochondrial) origin, and triggers the interferon response. The mechanisms of DNA recognition and cGAS–STING activation and signalling are now coming into focus, providing insights into the cellular functions of this pathway, including interferon-independent roles.

    • Karl-Peter Hopfner
    • Veit Hornung
    Review Article
  • Autophagy involves engulfment of cellular components into double-membrane vesicles called autophagosomes. The biogenesis of autophagosomes requires the cooperation of multiple proteins and lipids from various membrane sources. Our understanding of the molecular mechanisms of the initiation, growth, bending and closure of autophagosomal membranes is expanding at a rapid pace.

    • Hitoshi Nakatogawa
    Review Article
  • Circular RNAs, which are produced through back-splicing of exons, are emerging as key regulators of immune responses and cell proliferation. Recent studies have shed new light on the biogenesis and functions of circular RNAs, which include the modulation of transcription and splicing, and interference with microRNAs and other cellular signalling pathways.

    • Ling-Ling Chen
    Review Article
  • G-quadruplexes (G4s) are structures formed in guanine-rich DNA or RNA, which are linked to transcription, translation, chromatin biology, genome instability and RNA modifications. Recent studies connect G4 formation with cancer-cell lethality and indicate that G4s could be therapeutic targets.

    • Dhaval Varshney
    • Jochen Spiegel
    • Shankar Balasubramanian
    Review Article
  • In this Consensus Statement, the authors (on behalf of the EMT International Association) propose guidelines to define epithelial–mesenchymal transition, its phenotypic plasticity and the associated multiple intermediate epithelial–mesenchymal cell states. Clarification of nomenclature and definitions will help reduce misinterpretation of research data generated in different experimental model systems and promote cross-disciplinary collaboration.

    • Jing Yang
    • Parker Antin
    • Guojun Sheng
    Consensus Statement Open Access
  • Development and homeostasis are dependent on rapid cell turnover, achieved by the programmed death and subsequent engulfment and breakdown of cells, a process known as efferocytosis. Defects in efferocytosis have been linked to a wide range of diseases; ongoing research therefore aims to better understand efferocytosis processes so as to uncover new therapeutic targets.

    • Emilio Boada-Romero
    • Jennifer Martinez
    • Douglas R. Green
    Review Article
  • Telomere length is maintained by telomerase, which comprises a reverse transcriptase and a template RNA. Telomerase activity is disrupted in several genetic disorders, but is commonly increased in cancer. Recent studies have uncovered many regulatory mechanisms of telomerase and how telomerase upregulation in cancer is achieved.

    • Caitlin M. Roake
    • Steven E. Artandi
    Review Article
  • Cells maximize the repertoire of functions produced from their genome through introducing diversity at each stage of the gene expression process, including at the post-translational level. New advances in proteomics and interactomics have begun to shed light on the extent to which diversity is introduced on the proteome level and by the organization of proteins into modular interaction networks.

    • Isabell Bludau
    • Ruedi Aebersold
    Review Article
  • Reactive oxygen species (ROS) were originally associated with cellular damage and disease. However, ROS, notably hydrogen peroxide, at low physiological levels also engage in physiological signalling, supporting cellular responses and adaptation to changing environments and stress. Accordingly, controlling specific ROS-mediated signalling pathways offers new perspectives for a more refined redox medicine.

    • Helmut Sies
    • Dean P. Jones
    Review Article
  • The transcriptional response to hypoxia and the role of hypoxia inducible factors have been extensively studied. Yet, hypoxic cells also adapt to hypoxia by modulating protein synthesis, metabolism and nutrient uptake. Understanding these processes could shed light on pathologies associated with hypoxia, including cardiovascular diseases and cancer, and disease mechanisms, such as inflammation and wound repair.

    • Pearl Lee
    • Navdeep S. Chandel
    • M. Celeste Simon
    Review Article
  • The mechanical and dynamic properties of microtubules are determined by their complement of subunits, known as tubulin isotypes, and the post-translational modifications found on these isotypes. This concept is known as the ‘tubulin code’. The regulation of microtubules and microtubule-associated proteins by this code is critical for the correct function of a range of tissues. Consequently, recent studies have linked perturbation of the tubulin code to disease, including neurodegenerative diseases.

    • Carsten Janke
    • Maria M. Magiera
    Review Article
  • BRCA1 and its partner BARD1 support repair of double-strand breaks by homologous recombination and protect replication forks from damage. Recent studies have improved our understanding of the molecular mechanisms of these tumour-suppressive functions of BRCA1–BARD1 and how they are subverted in therapy-resistant cancers.

    • Madalena Tarsounas
    • Patrick Sung
    Review Article
  • Mitochondrial networks are dynamically remodelled via fusion, fission and ultrastructural changes to mitochondrial membranes. These mitochondrial membrane dynamics are tightly coupled to cell function, with morphological changes to mitochondria accompanying a multitude of processes as diverse as cell pluripotency, division, differentiation, senescence and death. Accordingly, disturbed dynamics of mitochondrial membranes are linked to severe human disorders.

    • Marta Giacomello
    • Aswin Pyakurel
    • Luca Scorrano
    Review Article