• Opinion |

    Although non-coding RNAs have roles in transcription and chromatin function, nascent pre-mRNA is usually considered to be passive during these processes. Recently identified interactions between nascent pre-mRNAs and regulatory proteins suggest that both types of RNA regulate transcription and chromatin function.

    • Lenka Skalska
    • , Manuel Beltran-Nebot
    • , Jernej Ule
    •  & Richard G. Jenner
  • Opinion |

    In animal cells, actin is dynamically distributed between multiple coexisting arrays. Carlier and Shekhar propose that a global treadmilling process — whereby the various actin networks grow and shrink depending on the local activity of actin regulators — establishes a steady-state concentration of actin monomers that supports this homeostatic actin turnover.

    • Marie-France Carlier
    •  & Shashank Shekhar
  • Opinion |

    The chemical modifications and structural features of mRNAs are highly dynamic. Together, they regulate the composition and function of the transcriptome by shaping RNA–protein interactions at different stages of the gene expression process.

    • Cole J.T. Lewis
    • , Tao Pan
    •  & Auinash Kalsotra
  • Opinion |

    The establishment of various coexisting actin networks supports a plethora of cellular processes and functions. How actin incorporation into these different networks is regulated to balance their growth and maintain homeostasis has remained elusive. Here, the authors propose that the internetwork competition for a limited pool of actin monomers underlies the homeostatic control of actin cytoskeleton organization.

    • Cristian Suarez
    •  & David R. Kovar
  • Opinion |

    Many proteins that canonically function in the cytosol can also localize to the nucleus. The authors propose that a distinct group of such proteins (which they name STRaNDs) engage in a particular mode of signal transduction, whereby in response to extracellular cues, the cytosolic protein transits to the nucleus and regulates gene expression without direct DNA binding.

    • Min Lu
    • , Mary R. Muers
    •  & Xin Lu
  • Opinion |

    Quante and Bird propose that the epigenome is modulated by the recruitment of cell type-specific DNA-binding proteins to short, abundant sequence motifs. The regulation of gene expression may thus be simplified by tuning gene expression in multigene blocks.

    • Timo Quante
    •  & Adrian Bird
  • Opinion |

    Members of the major facilitator superfamily are highly conserved transmembrane proteins that transport various small molecules, including nutrients, drugs, signalling molecules and waste products, across the plasma membrane. A novel model of their functional cycle provides insights into how these important transporters operate on the molecular level.

    • Esben M. Quistgaard
    • , Christian Löw
    • , Fatma Guettou
    •  & Pär Nordlund
  • Opinion |

    Catenins are typically considered to function at cell–cell junctions. However, it has recently become evident that multiple catenins can enter the nucleus and regulate gene expression. Thus, catenins might form complex networks, coupling membrane-associated signalling with transcriptional events.

    • Pierre D. McCrea
    •  & Cara J. Gottardi
  • Opinion |

    How endocytic pits are formed in clathrin- and caveolin-independent endocytosis remains poorly understood. However, recent insight suggests that different forms of clathrin-independent endocytosis might involve the actin-driven focusing of membrane constituents, the lectin–glycosphingolipid-dependent construction of endocytic nanoenvironments and the use of Bin–Amphiphysin–Rvs (BAR) domain proteins as scaffolding modules.

    • Ludger Johannes
    • , Robert G. Parton
    • , Patricia Bassereau
    •  & Satyajit Mayor
  • Opinion |

    Faithful chromosome segregation during mitosis depends on the bi-oriented attachment of chromosomes to spindle microtubules through their kinetochores. The precise regulation of kinetochore–microtubule attachment that ensures error-free mitosis may be explained by homeostatic principles involving receptors, a core control network, effectors and feedback control.

    • Kristina M. Godek
    • , Lilian Kabeche
    •  & Duane A. Compton
  • Opinion |

    Dishevelled, EGL-10 and pleckstrin (DEP) domains carry out diverse functions by using different binding interfaces with well-defined structural features. It is becoming apparent that DEP domains mainly function in the spatial and temporal control of diverse signal transduction events by interacting with various partners at the plasma membrane.

    • Sarah V. Consonni
    • , Madelon M. Maurice
    •  & Johannes L. Bos
  • Opinion |

    Proteome maintenance was thought to be controlled in a cell-autonomous manner. However, recent findings suggest that proteostasis can be systemically regulated. Protein-folding defects systemically activate proteostasis mechanisms through signalling pathways that coordinate stress responses among tissues, and this may also coordinate ageing rates between tissues.

    • Rebecca C. Taylor
    • , Kristen M. Berendzen
    •  & Andrew Dillin
  • Opinion |

    Cell death research was revitalized by the understanding that necrosis can occur in a regulated and genetically controlled manner. Although necroptosis is the most recognized form of regulated necrosis, other examples of this process have emerged. Understanding how these pathways are interconnected should enable regulated necrosis to be therapeutically targeted.

    • Tom Vanden Berghe
    • , Andreas Linkermann
    • , Sandrine Jouan-Lanhouet
    • , Henning Walczak
    •  & Peter Vandenabeele
  • Opinion |

    Autophagy was thought to be a purely cytosolic event. However, recent data highlight a role for the nucleus in autophagy regulation, showing that a complex network of histone modifications, microRNAs and transcription factors also control this process.

    • Jens Füllgrabe
    • , Daniel J. Klionsky
    •  & Bertrand Joseph
  • Opinion |

    Structural and mechanistic studies have revealed common features of the way in which RNA and proteins are prepared for degradation by the exosome and proteasome, respectively. By extrapolating from what has been learnt about the proteasome, we may gain increased understanding of how its RNA counterpart, the exosome, is assembled and controlled.

    • Debora L. Makino
    • , Felix Halbach
    •  & Elena Conti
  • Opinion |

    A growing list of membrane trafficking regulators, particularly those affecting clathrin-mediated endocytosis, have independent functions in mitosis. This repurposing may have arisen from the functional flexibility of the membrane trafficking machinery.

    • Stephen J. Royle
  • Opinion |

    Early mammalian blastocyst patterning involves symmetry breaking leading to lineage segregation. The classic models of lineage segregation cannot account for recent experimental data, and a new framework that regards the early mammalian embryo as a self-organizing system is put forward to explain these observations.

    • Sebastian Wennekamp
    • , Sven Mesecke
    • , François Nédélec
    •  & Takashi Hiiragi
  • Opinion |

    The function and regulation of poly(ADP-ribosyl)ation is partially understood. By contrast, little is known about intracellular mono(ADP-ribosyl)ation (MARylation) by ADP-ribosyl transferases. Recent findings indicate that MARylation regulates signalling and transcription by modifying key components in these processes, and that specific macrodomain-containing proteins 'read' and 'erase' this modification.

    • Karla L. H. Feijs
    • , Alexandra H. Forst
    • , Patricia Verheugd
    •  & Bernhard Lüscher
  • Opinion |

    The transmembrane protein Crumbs is known to maintain epithelial polarity and regulate Notch and Hippo signalling via its short intracellular domain. Recent evidence now suggests that its extracellular domain has a conserved and fundamental role in mediating homophilic Crumbs–Crumbs interactions at cell–cell junctions.

    • Barry J. Thompson
    • , Franck Pichaud
    •  & Katja Röper
  • Opinion |

    The distribution of partitioning defective (PAR) proteins into two domains on the membrane is a hallmark of cell polarity. Domain boundaries are set by mechanical, biochemical and biophysical signals, and the resulting PAR domains define areas of cytosol specialization. Physical studies are now contributing to the understanding of the mechanisms underlying polarity establishment by PAR proteins.

    • Carsten Hoege
    •  & Anthony A. Hyman
  • Opinion |

    Both microRNAs (miRNAs) and other small non-coding RNAs (ncRNAs) are induced by DNA breaks and have been linked to the DNA damage response. This interplay between ncRNAs and repair factors may help to ensure efficient DNA repair and maintenance of genome stability.

    • Dipanjan Chowdhury
    • , Young Eun Choi
    •  & Marie Eve Brault
  • Opinion |

    Myofilament length is a crucial parameter for efficient skeletal muscle contraction. Thin actin filament specification can be explained by a novel 'two-segment' model, whereby the filament consists of two concatenated segments that are of either constant or variable length. This model implicates that actin dynamics are subject to position-specific microregulation.

    • David S. Gokhin
    •  & Velia M. Fowler
  • Opinion |

    An increasing number of proteins have been discovered that evade turnover and instead are maintained over a cell's lifetime. Accumulation of damage in these long-lived proteins may contribute to the ageing process.

    • Brandon H. Toyama
    •  & Martin W. Hetzer
  • Opinion |

    Three surveillance pathways specialize in the degradation of mRNA molecules trapped in stalled translation complexes: the non-stop decay (NSD), the no-go decay (NGD) and the 18S-rRNA decay (18S-NRD) pathways. These quality control mechanisms degrade faulty mRNAs and contribute to maintaining the production of functional proteins.

    • Marc Graille
    •  & Bertrand Séraphin
  • Opinion |

    Research on the cadherin–junctional actin interaction has focused on how the two physically interact. However, the actin cytoskeleton is dynamic, regulated by a network of proteins, so a broader perspective that takes this into account may provide new insights on cadherin cell–cell contacts and on the role of cadherins in disease.

    • Aparna Ratheesh
    •  & Alpha S. Yap
  • Opinion |

    Forces transmitted through cell–cell and cell–extracellular matrix adhesions control cell fate decisions. But how are mechanical cues translated into gene expression programmes? The transcriptional regulators YAP and TAZ have arisen as convergence points of mechanical and biochemical signals.

    • Georg Halder
    • , Sirio Dupont
    •  & Stefano Piccolo
  • Opinion |

    Membrane trafficking relies on changes in membrane identity, which are determined by RAB GTPases and phosphoinositides. Coordinated regulation of RABs and phosphoinositides, which is achieved by direct physical and functional interactions between their regulatory enzymes, is emerging as a central mechanism to ensure membrane trafficking fidelity.

    • Steve Jean
    •  & Amy A. Kiger
  • Opinion |

    Metabolic signalling pathways and telomere shortening are both thought to, independently, have crucial roles in driving the ageing process. But links between these two processes suggest that they may converge on mitochondria to compromise energy maintenance, thereby driving ageing.

    • Ergün Sahin
    •  & Ronald A. DePinho
  • Opinion |

    Increasing evidence suggests that cell-to-cell communication in mammals can occur through the exchange of genetic information, mainly in the form of microRNAs (miRNAs). This exchange can be mediated by extracellular vesicles such as exosomes through intimate membrane contacts between donor and acceptor cells, or a combination of both.

    • Maria Mittelbrunn
    •  & Francisco Sánchez-Madrid
  • Opinion |

    Endocytic recycling, for some time considered to occur by default, is now emerging as an active sorting process. These studies are increasing our understanding of the physiological events that require recycling.

    • Victor W. Hsu
    • , Ming Bai
    •  & Jian Li
  • Opinion |

    Signalling is known to regulate metabolism, and it is becoming clear that this regulation is reciprocal, with signalling pathways being regulated by the availability of nutrient-sensitive modifications, such as acetylation and glycosylation. This tight link between signalling and metabolism allows cells to modulate their activities according to metabolic status.

    • Kathryn E. Wellen
    •  & Craig B. Thompson
  • Opinion |

    Satellite cells are a heterogeneous population of stem and progenitor cells with crucial roles in muscle repair and regeneration. Although paired-box 7 (PAX7) is necessary to maintain the undifferentiated stem cell state, a requirement for PAX7 in adult satellite cells was recently challenged and remains controversial.

    • Yu Xin Wang
    •  & Michael A. Rudnicki
  • Opinion |

    Although the multivesicular body (MVB) is classically defined as an intermediate that delivers material for lysosomal degradation, its role in the sequestration of glycogen synthase kinase 3 during WNT signalling has revealed a positive influence of this organelle in signalling control. This Opinion article proposes that this function of MVBs as a signalling organelle is physiologically relevant during development and may be common to diverse signalling pathways.

    • Radek Dobrowolski
    •  & Edward M. De Robertis
  • Opinion |

    Caspase 8 initiates apoptosis but also has non-apoptotic roles during embryonic development and for immune cell proliferation. Recent findings indicate that the non-apoptotic functions of caspase 8 are defined by the suppression of receptor-interacting protein kinase 3 (RIPK3), a kinase that triggers programmed necrosis.

    • Andrew Oberst
    •  & Douglas R. Green
  • Opinion |

    The phosphodiesterase autotaxin (ATX) produces the lipid mediator lysophosphatidic acid (LPA) to regulate diverse processes, including cell migration and proliferation. Studies of the structure of ATX may shed new light on how ATX recognizes its substrates and associates with the cell surface to promote specificity in LPA signalling.

    • Wouter H. Moolenaar
    •  & Anastassis Perrakis
  • Opinion |

    Differentiated cells can become pluripotent through reprogramming by nuclear transfer, cell fusion and induced pluripotent stem cell technology. The characteristics of reprogramming by nuclear transfer and cell fusion suggest that they occur in a deterministic, rather than a stochastic, manner.

    • Jerome Jullien
    • , Vincent Pasque
    • , Richard P. Halley-Stott
    • , Kei Miyamoto
    •  & J. B. Gurdon
  • Opinion |

    The production of mature and export-competent messenger ribonucleoproteins (mRNPs) is a multistep process that is regulated in a spatial and temporal manner. Recent studies suggest that post-translational modifications play a part in coordinating the co-transcriptional assembly, remodelling and export of mRNP complexes through nuclear pores.

    • Evelina Tutucci
    •  & Françoise Stutz
  • Opinion |

    Alan Turing showed that spatial patterns can be generated when two morphogens diffuse and react. Although he realized the importance of mechanics, it has only recently become clear that mechanical processes (forces and flows generated by motors) can also contribute to patterning when coupled to chemical reactions.

    • Jonathon Howard
    • , Stephan W. Grill
    •  & Justin S. Bois
  • Opinion |

    The improper distribution of chromosomes during mitosis can contribute to malignant transformation. Higher eukaryotes have developed strategies for eliminating mitosis-incompetent cells, one of which is mitotic catastrophe. From a functional perspective, mitotic catastrophe can be defined as an oncosuppressive mechanism that precedes (and is distinct from) apoptosis, necrosis or senescence.

    • Ilio Vitale
    • , Lorenzo Galluzzi
    • , Maria Castedo
    •  & Guido Kroemer
  • Opinion |

    The p53 family of transcription factors have diverse roles during development and in cancer. However, there is increasing evidence that their ancestral function may have been to regulate unique aspects of maternal fertility.

    • Arnold J. Levine
    • , Richard Tomasini
    • , Frank D. McKeon
    • , Tak W. Mak
    •  & Gerry Melino
  • Opinion |

    Computational morphodynamics has provided great insights into the highly dynamic process of plant development. This is because it combines live imaging to observe development as it happens, image processing to extract data, and computational modelling to test hypotheses against quantitative information.

    • Adrienne H. K. Roeder
    • , Paul T. Tarr
    • , Cory Tobin
    • , Xiaolan Zhang
    • , Vijay Chickarmane
    • , Alexandre Cunha
    •  & Elliot M. Meyerowitz
  • Opinion |

    Unlike somatic cells, stem cells persist throughout life, which may increase their risk of accumulating DNA damage. recent studies indicate that stem cells use different mechanisms (such as the error-prone non-homologous end joining pathway) from somatic cells to maintain genomic integrity, which could have deleterious consequences for their long-term function.

    • Pankaj K. Mandal
    • , Cédric Blanpain
    •  & Derrick J. Rossi
  • Opinion |

    Mesenchymal stem cells (MSCs) are multipotent progenitors derived from tissue stroma that differentiate into adipocytes, chondrocytes and osteoblasts when expandedin vitro. Although the properties of the in vitro-expanded progeny are well defined, the in vivobiology of MSCs is only just beginning to be elucidated.

    • César Nombela-Arrieta
    • , Jerome Ritz
    •  & Leslie E. Silberstein
  • Opinion |

    Single-cell measurements and lineage-tracing experiments are revealing that cell-to-cell variability is often the result of deterministic processes, despite the existence of intrinsic noise in molecular networks. As this determinism usually represents uncharacterized molecular regulatory mechanisms, cell-to-cell variability should be studied as a discipline of molecular cell biology.

    • Berend Snijder
    •  & Lucas Pelkmans
  • Opinion |

    The mechanisms regulating the import of proteins into peroxisomes share surprising similarities with those controlling the degradation of proteins at the endoplasmic reticulum. These unexpected parallels may result from the common molecular machinery used to tag substrates and drive their removal from the membrane.

    • Wolfgang Schliebs
    • , Wolfgang Girzalsky
    •  & Ralf Erdmann
  • Opinion |

    Aminoacyl tRNA synthetases (aaRSs) have progressively added domains and motifs that have no connection to aminoacylation. These additions equip aaRSs with new functions and correlate with the appearance of new biological processes (such as a circulatory system) during the course of evolution.

    • Min Guo
    • , Xiang-Lei Yang
    •  & Paul Schimmel
  • Opinion |

    Recent studies suggest that the spindle matrix provides a conserved strategy to coordinate the segregation of genetic material and the partitioning of other cellular contents in open, partially open and closed mitosis.

    • Yixian Zheng
  • Opinion |

    Current descriptions of eukaryotic chemotaxis focus on how extracellular signals (chemoattractants) cause new pseudopods to form. However, reinterpretation of recent data suggests a 'pseudopod-centred' explanation, whereby most pseudopods form without exogenous signals and chemoattractants only bias the position and rate of pseudopod growth.

    • Robert H. Insall
  • Opinion |

    GW182 proteins are key components of microRNA silencing complexes in animals, although their precise molecular function has been poorly understood. Recent findings indicate that they promote gene silencing by interfering with cytoplasmic poly(A)-binding protein 1 (PABPC1) function during translation and mRNA stabilization — a mode of action similar to that of PABP-interacting protein 2 (PAIP2).

    • Felix Tritschler
    • , Eric Huntzinger
    •  & Elisa Izaurralde
  • Opinion |

    Neurodegenerative diseases are associated with the accumulation of intracellular or extracellular protein aggregates that form because of protein misfolding. These aggregates are capable of crossing cellular membranes and can thereby directly contribute to the propagation of neurodegenerative disease pathogenesis, which might spread in a 'prion-like' manner.

    • Patrik Brundin
    • , Ronald Melki
    •  & Ron Kopito