Molecular biology

  • Article
    | Open Access

    An analysis of MitCOM—a comprehensive resource for the identification, organization and interaction of mitochondrial machineries and pathways in yeast—identifies a constitutive pathway for the removal of preproteins.

    • Uwe Schulte
    • , Fabian den Brave
    •  & Thomas Becker
  • Article |

    Mass spectrometry and structural studies demonstrate the specific changes in protein composition that accompany the transition of ribosomes in zebrafish and Xenopus eggs from a dormant to an active state during early embryogenesis.

    • Friederike Leesch
    • , Laura Lorenzo-Orts
    •  & Andrea Pauli
  • Article |

    Analyses of in-frame stop codons in protein-coding genes of Blastocrithidia nonstop with all three stop codons reassigned reveal a mechanism for UGA reassignment in eukaryotes involving shortening of the tRNA anticodon stem and a mutant eRF1 release factor.

    • Ambar Kachale
    • , Zuzana Pavlíková
    •  & Julius Lukeš
  • Article |

    Structural studies of Escherichia coli transcription intrinsic termination complexes representing distinct intermediates using cryo-electron microscopy provide insights into the steps and mechanism of transcription termination.

    • Linlin You
    • , Expery O. Omollo
    •  & Yu Zhang
  • Article
    | Open Access

    RNA targeting by the Sulfuricurvum type V single-effector nuclease SuCas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA—after recognition of an RNA target through an activating protospacer-flanking sequence, SuCas12a2 efficiently degrades ssRNA, ssDNA and dsDNA.

    • Oleg Dmytrenko
    • , Gina C. Neumann
    •  & Chase L. Beisel
  • Article |

    Structures of the human METTL1–WDR4 complex are revealed, providing molecular insights into substrate recognition, modification and catalytic regulation by the N7-methylguanosine methyltransferase complex.

    • Jiazhi Li
    • , Longfei Wang
    •  & Richard I. Gregory
  • Article
    | Open Access

    Evolutionary analyses of single-nucleus transcriptome data for testes from 11 species are reported, illuminating the molecular evolution of spermatogenesis and associated forces, and providing a resource for investigating the testis across mammals.

    • Florent Murat
    • , Noe Mbengue
    •  & Henrik Kaessmann
  • Article |

    RibosomeST—a ribosome with a specialized nascent polypeptide exit tunnel—cotranslationally regulates the folding of a subset of male germ-cell-specific proteins that are essential for the formation of sperm.

    • Huiling Li
    • , Yangao Huo
    •  & Jiahao Sha
  • Article |

    Results are presented that indicate that alterations to gene regulatory three-dimensional architecture are a critical mechanism that enables structural variant-based oncogene activation in cancer genomes and sheds light on the essential elements for such gene activation events.

    • Zhichao Xu
    • , Dong-Sung Lee
    •  & Jesse R. Dixon
  • Article
    | Open Access

    A non-genetic mechanism of sex determination in the human malaria parasite, Plasmodium falciparum, is described, and the male development 1 gene is identified as a potential target for interventions that block malaria transmission.

    • A. R. Gomes
    • , A. Marin-Menendez
    •  & A. M. Talman
  • Article |

    Provora is an ancient supergroup of microbial predators that are genetically, morphologically and behaviourally distinct from other eukaryotes, and comprise two divergent clades of predators—Nebulidia and Nibbleridia—that differ fundamentally in ultrastructure, behaviour and gene content.

    • Denis V. Tikhonenkov
    • , Kirill V. Mikhailov
    •  & Patrick J. Keeling
  • Article
    | Open Access

    Structural studies of the CRISPR-associated transposon comprising Cas12k, TnsC, TnsB and TniQ from Scytonema hofmannii using cryo-electron microscopy reveal insights into the architecture and mechanism of RNA-guided DNA transposition.

    • Jung-Un Park
    • , Amy Wei-Lun Tsai
    •  & Elizabeth H. Kellogg
  • Article
    | Open Access

    The cryogenic-electron microscopy structure of the D. thermocuniculi IsrB protein in complex with its cognate ωRNA and a target DNA shows that the RNA-dominant IsrB effector complex shares a common scaffold with the protein-dominant Cas9 effector complex.

    • Seiichi Hirano
    • , Kalli Kappel
    •  & Feng Zhang
  • Article |

    RNA sensing-mediated payload expression provides a specific, versatile, simple and generalizable means of detecting and manipulating animal cells with broad potential applications.

    • Yongjun Qian
    • , Jiayun Li
    •  & Z. Josh Huang
  • Article |

    The cryo-electron microscopy structure of NuA4 from Saccharomyces cerevisiae bound to the nucleosome illustrates how NuA4 is assembled and provides mechanistic insights into nucleosome recognition and transcription co-activation by a histone acetyltransferase.

    • Keke Qu
    • , Kangjing Chen
    •  & Zhucheng Chen
  • 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