Browse Articles

  • 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
  • Research Highlight |

    Nature Reviews Molecular Cell Biology congratulates the winners of the 2018 Lasker Foundation Awards.

    • Paulina Strzyz
  • 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
  • Journal Club |

    The introduction of DNA-chain terminators for sequencing by Fred Sanger enabled the early genome sequencing projects.

    • George G. Brownlee
  • Research Highlight |

    The kinase ATR senses the completion of DNA replication and controls the S/G2 cell-cycle transition.

    • Michelle Trenkmann
  • Research Highlight |

    Direct demonstration that mutations in intrinsically disordered regions modulate protein–protein interaction networks, which may cause disease.

    • Paulina Strzyz
  • 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
  • Research Highlight |

    3′uridylation by TUT4 and TUT7 is shown as a post-transcriptional mechanism restricting retrotransposition of LINE-1 elements and also replication of animal RNA viruses.

    • Paulina Strzyz
  • 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
  • Research Highlight |

    A study reports that CRISPR–Cas9 induces extensive on-target mutagenesis in mouse and human cells, calling for greater caution when using it in clinical contexts.

    • Kim Baumann
  • Research Highlight |

    Poly(dA:dT) tracts characterize strong DNA replication origins in mammals and cause replication-fork collapse and DNA breaks that underlie the expression of fragile sites.

    • Eytan Zlotorynski
  • 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
  • Research Highlight |

    A new study in Nature identifies a molecular axis linking diabetes to cancer, whereby AMPK, which is inhibited in high glucose conditions, regulates the stability of TET2 DNA demethylase, thereby impacting DNA methylation and gene expression.

    • Paulina Strzyz
  • Journal Club |

    Ueli Schibler explains why the phenotype of a mutation in a codon of the ‘21st amino acid’ selenium cysteine was unexpectedly specific.

    • Ueli Schibler
  • Research Highlight |

    Eliminating senescent cells by administering senolytic drugs can improve healthspan and lifespan in mice.

    • Kim Baumann
  • 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
  • Journal Club |

    Rebecca Taylor discusses the elegance and importance of early discoveries from the Walter laboratory on the unfolded protein response, and why they have become landmark studies.

    • Rebecca C. Taylor
  • Comment |

    G protein coupled receptors (GPCRs) transmit a variety of signals, mostly by engaging G proteins, but G protein-independent signalling through arrestins has also been demonstrated. Based on recent experimental evidence, Gutkind and Kostenis argue that arrestins serve as important signal modulators instead of as independent signal transducers.

    • J. Silvio Gutkind
    •  & Evi Kostenis
  • Journal Club |

    Senescent cells secrete a multitude of factors that modulate their local environment — a phenomenon known as senescence-associated secretory phenotype (SASP). David Bernard highlights that the SASP secretome can be flexibly regulated, resulting in different types of SASP, which contributes to the versatility of responses triggered by senescent cells.

    • David Bernard
  • 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
  • Research Highlight |

    The chromatin remodelling complex NuRD fine-tunes gene expression by modulating nucleosome density at gene regulatory elements.

    • Anne Mirabella
  • Research Highlight |

    Many eukaryotic proteins, including key transcription regulators, contain intrinsically disordered regions (IDRs), which serve as flexible interaction platforms. The molecular understanding of IDR-based interactions is now emerging, providing new insights into how IDRs promote protein compartmentalization and/or phase separation and how these processes regulate gene expression.

    • Paulina Strzyz
  • Research Highlight |

    Two independent studies now show that polymerization of branched actin at DNA double-strand breaks (DSBs) mediates chromatin dynamics associated with homology-directed repair and is required for a robust and error-free DSB repair process.

    • Paulina Strzyz
  • Research Highlight |

    The inner nuclear membrane is metabolically active and generates lipid droplets.

    • Kim Baumann
  • 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
  • Research Highlight |

    MicroRNAs derived from a virus and teratocytes of a parasitic wasp are expressed in a host moth and delay its development by inhibiting the ecdysone receptor.

    • Eytan Zlotorynski
  • 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
  • Research Highlight |

    Increased shortening of RNA 3′ untranslated regions associated with tumorigenic transformation interferes with competing endogenous RNA (ceRNA) networks, which results in trans-repression of tumour suppressors through microRNA-mediated silencing.

    • Paulina Strzyz
  • Research Highlight |

    Muscle stem cells produce collagen V, which becomes a component of the niche that promotes their quiescence.

    • Kim Baumann
  • 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
  • Comment |

    Biomolecules can phase separate and form condensates that have roles in diverse cellular processes and contexts. Michnick and Bergeron-Sandoval comment on this rapidly progressing field and envisage that the study of biological phase separation will bring new understanding of cell and developmental biology.

    • Stephen W. Michnick
    •  & Louis-Philippe Bergeron-Sandoval
  • Research Highlight |

    The spindle checkpoint complex BUB3–BUB1 facilitates telomere replication through recruitment of the helicase BLM, and the telomere capping protein TRF2 promotes replication at pericentromeres by recruiting the helicase RTEL1; both helicases resolve G-quadruplex structures.

    • Eytan Zlotorynski
  • Comment |

    Cellular organelles extensively communicate with each other by close interactions, known as membrane contact sites. Schuldiner and Bohnert comment on the progress of this rapidly developing field, highlighting that the complexity of interactions at membrane contact sites is only now starting to emerge.

    • Maria Bohnert
    •  & Maya Schuldiner
  • 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
  • Journal Club |

    Kikuë Tachibana discusses some of the key findings of the seminal works of Sir John Gurdon on nuclear reprogramming and how, by being examples of scientific rigour, they have inspired her own research.

    • Kikuë Tachibana
  • 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
  • Research Highlight |

    EpiTOF characterized the epigenetic landscape of various types of single immune cells and revealed that their heterogeneity increases with age.

    • Grant Otto