Browse Articles

  • Article |

    A screen for C. elegans antiviral-defense genes identifies a homolog of the mammalian TUT4(7) terminal uridylyltransferase genes and leads to the discovery of 3′-terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.

    • Jérémie Le Pen
    • , Hongbing Jiang
    • , Tomás Di Domenico
    • , Emma Kneuss
    • , Joanna Kosałka
    • , Christian Leung
    • , Marcos Morgan
    • , Christian Much
    • , Konrad L. M. Rudolph
    • , Anton J. Enright
    • , Dónal O’Carroll
    • , David Wang
    •  & Eric A. Miska
  • Article |

    A set of GFP fusions with as few as 12 residues appended to the C terminus is shown to assemble into filaments in E. coli. Crystal structures reveal a mechanism termed ‘runaway domain coupling’ and illustrate how protein filament formation can evolve.

    • Laura McPartland
    • , Danielle M. Heller
    • , David S. Eisenberg
    • , Ann Hochschild
    •  & Michael R. Sawaya
  • Article |

    Time-resolved X-ray crystal structures of RNA hydrolysis by RNase H1 reveal that cations in addition to the two canonical Mg2+ ions position the reactants in the active site and enable catalysis.

    • Nadine L. Samara
    •  & Wei Yang
  • Article |

    Cell-based and in vitro analyses reveal that BRD4 functionally associates with eRNAs and that BRD4 bromodomains, through eRNA interactions, promote BRD4 binding at mutant p53-targeted enhancers to augment enhancer activation and tumor promoting gene expression.

    • Homa Rahnamoun
    • , Jihoon Lee
    • , Zhengxi Sun
    • , Hanbin Lu
    • , Kristen M. Ramsey
    • , Elizabeth A. Komives
    •  & Shannon M. Lauberth
  • Article |

    Cryo-EM structures of the RAG endonuclease in complex with intact DNA substrates reveal that DNA melting is the first step in V(D)J recombination, a mechanism potentially conserved in retroviral integration and DNA transposition.

    • Heng Ru
    • , Wei Mi
    • , Pengfei Zhang
    • , Frederick W. Alt
    • , David G. Schatz
    • , Maofu Liao
    •  & Hao Wu
  • News & Views |

    The effects of RNA secondary structure on translation have been well recognized; however, the global interplay between both in a dynamic cellular system is poorly understood. Beaudoin, Giraldez and colleagues have analyzed RNA structure dynamics during zebrafish embryonic development and have found that the ribosome unzips mRNA secondary structure during translation, thus leading to a global decrease of structure in highly translated transcripts. Furthermore, the authors establish RNA structure in the 3′ untranslated regions of mRNAs as a major regulator of transcript stability in this context.

    • Marianne C. Kramer
    •  & Brian D. Gregory
  • News & Views |

    The mechanism underlying CCG-repeat expansions in patients with fragile X premutation is not well understood. Using a new experimental system in mammalian cells, a study in this issue reports that break-induced replication has a role in CGG-repeat instability.

    • Madhura Deshpande
    •  & Jeannine Gerhardt
  • News & Views |

    A series of new cryo-EM structures reveals a surprising twist in how the RAG complex initiates V(D)J recombination. The initial complex with substrate DNA adopts two conformations: in one, the DNA is relatively undistorted but the scissile phosphate is far from the active site, and in the other the DNA is partially melted and unwound by half a turn, which allows the scissile phosphate to dock into the active site. Similar pre-catalysis DNA melting may occur with other DDE recombinases, for which equivalent complexes with uncleaved substrate DNA are not yet available.

    • Fred Dyda
    •  & Phoebe A. Rice
  • Article |

    The mitochondrial fission dynamin (Dnm1) from an algae is captured in a closed conformation, with the GTPase domain compacted against the stalk. This work indicates that formation of the closed conformation may contribute to membrane fission.

    • Olga Bohuszewicz
    •  & Harry H. Low
  • Article |

    Characterization of mRNA structure during the zebrafish maternal-to-zygotic transition identifies the ribosome as a major RNA structure remodeler in vivo and reveals that structural dynamics can affect gene expression, partly by modulating miRNA activity.

    • Jean-Denis Beaudoin
    • , Eva Maria Novoa
    • , Charles E. Vejnar
    • , Valeria Yartseva
    • , Carter M. Takacs
    • , Manolis Kellis
    •  & Antonio J. Giraldez
  • News & Views |

    Under steady-state conditions, the E3 ubiquitin ligase Parkin is localized to the cytosol in an autoinhibited state. Two recent studies describe the mechanism of Parkin activation by phosphorylation via structural rearrangement of the Ubl and RING2 domains, explaining how the RING2 domain is released from the core of Parkin to allow for ubiquitination of its substrates.

    • François Le Guerroué
    •  & Richard J. Youle
  • News & Views |

    In a stress-free environment, the histone binding function of 53BP1 is inhibited by TIRR, but upon DNA damage 53BP1 is recruited to chromatin and promotes DNA repair. New structural studies provide insights into the mechanisms underlying 53BP1 inhibition and activation. TIRR physically blocks the methyl-lysine histone-binding site of Tudors, and RNA binding by TIRR alleviates this block.

    • Yi Zhang
    •  & Tatiana G. Kutateladze
  • Article |

    Cryo-EM structure of the Salmonella Typhimurium FliP–FliQ–FliR complex identifies this export gate as a core component of the periplasmic portion of the type III secretion system.

    • Lucas Kuhlen
    • , Patrizia Abrusci
    • , Steven Johnson
    • , Joseph Gault
    • , Justin Deme
    • , Joseph Caesar
    • , Tobias Dietsche
    • , Mehari Tesfazgi Mebrhatu
    • , Tariq Ganief
    • , Boris Macek
    • , Samuel Wagner
    • , Carol V. Robinson
    •  & Susan M. Lea
  • Article |

    Structures of Cdc48 with heterodimeric cofactor Ufd1–Npl4 reveal the location of Npl4's MPN domain above Cdc48’s central pore, thus suggesting how Npl4 engages with polyubiquitinated substrates and promotes their translocation into the ATPase.

    • Nicholas O. Bodnar
    • , Kelly H. Kim
    • , Zhejian Ji
    • , Thomas E. Wales
    • , Vladimir Svetlov
    • , Evgeny Nudler
    • , John R. Engen
    • , Thomas Walz
    •  & Tom A. Rapoport
  • Article |

    Structural and functional dissection of the TIRR–53BP1 complex shows that TIRR acts as a regulatory switch that blocks 53BP1 binding to chromatin to direct DNA repair, and it releases 53BP1 in response to DNA damage by binding RNA.

    • Maria Victoria Botuyan
    • , Gaofeng Cui
    • , Pascal Drané
    • , Catarina Oliveira
    • , Alexandre Detappe
    • , Marie Eve Brault
    • , Nishita Parnandi
    • , Shweta Chaubey
    • , James R. Thompson
    • , Benoît Bragantini
    • , Debiao Zhao
    • , J. Ross Chapman
    • , Dipanjan Chowdhury
    •  & Georges Mer