Molecular biology

  • Article |

    The nuclear mitotic apparatus protein NuMA helps to protect genes from oxidative damage by occupying regions around transcription start sites, binding DNA repair factors and promoting transcription following damage.

    • Swagat Ray
    • , Arwa A. Abugable
    •  & Sherif F. El-Khamisy
  • Article
    | Open Access

    Cryo-electron tomography is used to reveal the structural dynamics and functional diversity of translating ribosomes in Mycoplasma pneumoniae, providing insight into the translation elongation cycle inside cells and how it is reshaped by antibiotics.

    • Liang Xue
    • , Swantje Lenz
    •  & Julia Mahamid
  • Article |

    CDK11 associates with SF3B1 and phosphorylates threonine residues at the N terminus of SF3B1 during spliceosome activation, and the inhibition of CDK11 blocks the activation and leads to widespread intron retention and the accumulation of non-functional spliceosomes on pre-mRNAs and chromatin.

    • Milan Hluchý
    • , Pavla Gajdušková
    •  & Dalibor Blazek
  • Article |

    Cryogenic electron microscopy analyses reveal a new, compact structure of telomeric chromatin, providing mechanistic insight into telomere maintenance and function.

    • Aghil Soman
    • , Sook Yi Wong
    •  & Lars Nordenskiöld
  • Article
    | Open Access

    The structures of single COOLAIR RNA isoforms change in abundance and shape in response to external conditions; structural mutation of these isoforms altered FLC expression and flowering time, consistent with a regulatory role of the COOLAIR structure in FLC transcription.

    • Minglei Yang
    • , Pan Zhu
    •  & Yiliang Ding
  • Article
    | Open Access

    Live-seq, a single-cell transcriptome profiling approach that preserves cell viability during RNA extraction using fluidic force microscopy, can address a range of biological questions by transforming scRNA-seq from an end-point to a temporal analysis approach.

    • Wanze Chen
    • , Orane Guillaume-Gentil
    •  & Bart Deplancke
  • Article |

    A time-resolved high-resolution map of human cardiac remodelling after myocardial infarction, integrating single-cell transcriptomic, chromatin accessibility and spatial transcriptomic data, provides a valuable resource for the field.

    • Christoph Kuppe
    • , Ricardo O. Ramirez Flores
    •  & Rafael Kramann
  • Article |

    cis-RNA editing quantitative trait loci, which are associated with immunogenic double-stranded RNAs, underlie genome-wide association study variants in common autoimmune and inflammatory diseases.

    • Qin Li
    • , Michael J. Gloudemans
    •  & Jin Billy Li
  • Article
    | Open Access

    The Polα–primase-associated CST complex organizes telomeric C-strand DNA synthesis, and, in combination with telomerase, it carries out complete replication of the single-stranded DNA overhang found at human telomeres.

    • Arthur J. Zaug
    • , Karen J. Goodrich
    •  & Thomas R. Cech
  • Article
    | Open Access

    The evolutionarily conserved RNA-binding protein GTSF1 and its homologues interact with members of the PIWI class of Argonaute proteins, increasing the efficiency of the RNA-cleaving activity of PIWI proteins, an essential function across the animal kingdom.

    • Amena Arif
    • , Shannon Bailey
    •  & Phillip D. Zamore
  • Article
    | Open Access

    Structures of the Dcr-2–Loqs-PD complex while it is processing a double-stranded RNA (dsRNA) substrate elucidate the interactions between Dcr-2 and Loqs-PD, and show that Dcr-2 undergoes substantial conformational changes during a dsRNA-processing cycle.

    • Shichen Su
    • , Jia Wang
    •  & Jinbiao Ma
  • Article
    | Open Access

    Cryo-electron microscopy structures of Drosophila Dicer-2–R2D2 complexes with and without small interfering RNA reveal how the RNA is presented to Argonaute in the correct orientation for viral gene silencing.

    • Sonomi Yamaguchi
    • , Masahiro Naganuma
    •  & Osamu Nureki
  • Article |

    Single-molecule spectroscopy and structural studies were used to examine the dynamics of association of eIF1A and eIF5B with the human translation initiation complex and their role in presenting tRNA to the complex to initiate translation.

    • Christopher P. Lapointe
    • , Rosslyn Grosely
    •  & Joseph D. Puglisi
  • Article |

    Treatment with neoadjuvant BRAF/MEK-targeted therapy results in higher rates of major pathological response in female compared with male patients with melanoma, and pharmacological inhibition of androgen receptor signalling improved the responses of male and female mice to BRAF/MEK-targeted therapy.

    • Christopher P. Vellano
    • , Michael G. White
    •  & Jennifer A. Wargo
  • Article
    | Open Access

    Cryo-electron microscopy structures of the sequential assembly of the CMG replicative helicase on a chromatinized origin of replication provide insights into the mechanism through which DNA melting is initiated by ATP binding.

    • Jacob S. Lewis
    • , Marta H. Gross
    •  & Alessandro Costa
  • Article
    | Open Access

    A study shows that the three-dimensional conformation of the human genome influences the positioning of DNA replication initiation zones, highlighting cohesin-mediated loop anchors as essential determinants of their precise location.

    • Daniel J. Emerson
    • , Peiyao A. Zhao
    •  & Jennifer E. Phillips-Cremins
  • Article |

    The systematic categorization of human enhancers by their cofactor dependencies provides a conceptual framework to understand the sequence and chromatin diversity of enhancers and their roles in different gene-regulatory programmes.

    • Christoph Neumayr
    • , Vanja Haberle
    •  & Alexander Stark
  • Article |

    A new high-throughput assay applied to 1,000 enhancers and 1,000 promoters in human cells reveals how different classes of enhancers and promoters control RNA expression.

    • Drew T. Bergman
    • , Thouis R. Jones
    •  & Jesse M. Engreitz
  • Article |

    Characterization of Gibbin, encoded by AHDC1, offers insights into the epidermal and mesodermal patterning phenotypes seen in Xia–Gibbs and related syndromes in humans, which derive from abnormal mesoderm maturation as a result of gene-specific DNA methylation decisions.

    • Ann Collier
    • , Angela Liu
    •  & Anthony E. Oro
  • Article
    | Open Access

    Single-nucleus Hi-C of embryos, polymer simulations and single-molecule imaging collectively reveal that MCM complexes influence genome folding and gene expression by impeding DNA loop extrusion.

    • Bart J. H. Dequeker
    • , Matthias J. Scherr
    •  & Kikuë Tachibana
  • Article |

    In Drosophila, there are extensive physical and functional associations of distant paralogous genes, including co-regulation by shared enhancers and co-transcriptional initiation over distances of nearly 250 kilobases.

    • Michal Levo
    • , João Raimundo
    •  & Michael S. Levine
  • Article |

    The molecular determinants for primer synthesis are identified within the catalytic domain of primase-polymerase enzymes, elucidating the mechanisms underlying initiation of primer synthesis.

    • Arthur W. H. Li
    • , Katerina Zabrady
    •  & Aidan J. Doherty
  • Article |

    Herpesvirus microRNAs interfere directly with host cell microRNA processing, thereby disrupting mitochondrial architecture, evading intrinsic host defences and driving the switch from latent to lytic infection.

    • Thomas Hennig
    • , Archana B. Prusty
    •  & Bhupesh K. Prusty
  • Article
    | Open Access

    A study maps neuronal genomic targets of oestrogen receptor-α and shows how they coordinate brain sexual differentiation, concluding that the genome remains responsive to hormonal changes after structural dimorphisms have been established.

    • B. Gegenhuber
    • , M. V. Wu
    •  & J. Tollkuhn
  • Article
    | Open Access

    Experiments in yeast show that introns have a role in inducing phenotypic heterogeneity and that intron-mediated regulation of ribosomal proteins confers a fitness advantage by enabling yeast populations to diversify under nutrient-scarce conditions.

    • Martin Lukačišin
    • , Adriana Espinosa-Cantú
    •  & Tobias Bollenbach
  • Article |

    Analyses of single-cell whole-genome sequencing data show that somatic mutations are increased in the brain of individuals with Alzheimer’s disease compared to neurotypical individuals, with a pattern of genomic damage distinct from that of normal ageing.

    • Michael B. Miller
    • , August Yue Huang
    •  & Christopher A. Walsh
  • Article
    | Open Access

    The transcriptional effect of an enhancer depends on its contact probabilities with the promoter through a nonlinear relationship, and enhancer strength determines absolute transcription levels as well as the sensitivity of a promoter to CTCF-mediated transcriptional insulation.

    • Jessica Zuin
    • , Gregory Roth
    •  & Luca Giorgetti
  • Article |

    Integrated structure–function studies show that transcription-coupled DNA repair (TCR)—rather than global genomic repair—is responsible for most chromosomal repair events in bacteria, and that TCR mainly occurs independently of the Mfd translocase.

    • Binod K. Bharati
    • , Manjunath Gowder
    •  & Evgeny Nudler