Browse Articles

  • News & Views |

    Epigenetic memory of silent chromatin often requires robust feedback loops between factors processing small non-coding RNAs and enzymes involved in heterochromatin assembly. A study published in Molecular Cell now demonstrates that these feedback loops can persist in a phenotypically neutral state even when gene expression is reactivated, and that they maintain the potential to reinstall heterochromatin in later generations when conditions change.

    • Matías Capella
    •  & Sigurd Braun
  • Article |

    Chris Garcia, David Baker and colleagues use a computational approach to develop designed repeat protein binders (DRPBs), which function as human Frizzled (Fz) subtype-selective antagonists and enable identification of Fz subtypes active in different organs.

    • Luke T. Dang
    • , Yi Miao
    • , Andrew Ha
    • , Kanako Yuki
    • , Keunwan Park
    • , Claudia Y. Janda
    • , Kevin M. Jude
    • , Kritika Mohan
    • , Nhi Ha
    • , Mario Vallon
    • , Jenny Yuan
    • , José G. Vilches-Moure
    • , Calvin J. Kuo
    • , K. Christopher Garcia
    •  & David Baker
  • Article |

    KMT9, a new histone lysine methyltransferase targeting H4K12, is enriched at promoters of genes encoding molecules involved in the cell cycle and controls the growth of androgen receptor–dependent and castration- and enzalutamide-resistant prostate cancer cells and xenograft tumors.

    • Eric Metzger
    • , Sheng Wang
    • , Sylvia Urban
    • , Dominica Willmann
    • , Andreas Schmidt
    • , Anne Offermann
    • , Anita Allen
    • , Manuela Sum
    • , Nadine Obier
    • , Félicie Cottard
    • , Svenja Ulferts
    • , Bogdan-Tiberius Preca
    • , Bianca Hermann
    • , Jochen Maurer
    • , Holger Greschik
    • , Veit Hornung
    • , Oliver Einsle
    • , Sven Perner
    • , Axel Imhof
    • , Manfred Jung
    •  & Roland Schüle
  • Resource |

    A quantitative atlas of RNA m5C sites in human and mouse tissues based on a new discovery pipeline allows the identification of sequence motifs and structural features associated with the modification and provides a resource for future studies.

    • Tao Huang
    • , Wanying Chen
    • , Jianheng Liu
    • , Nannan Gu
    •  & Rui Zhang
  • Comment |

    The long non-coding RNA Xist induces heterochromatinization of the X chromosome by recruiting repressive protein complexes to chromatin. Here we gather evidence, from the literature and from computational analyses, showing that Xist assemblies are similar in size, shape and composition to phase-separated condensates, such as paraspeckles and stress granules. Given the progressive sequestration of Xist’s binding partners during X-chromosome inactivation, we formulate the hypothesis that Xist uses phase separation to perform its function.

    • Andrea Cerase
    • , Alexandros Armaos
    • , Christoph Neumayer
    • , Philip Avner
    • , Mitchell Guttman
    •  & Gian Gaetano Tartaglia
  • News & Views |

    Cytosine methylation (m5C) is one of the more disputed base modifications of the epitranscriptome, mostly because current methods for detection are prone to artifacts. A new approach to increase detection accuracy reveals intriguing evidence of a role for the tRNA methyltransferase NSUN2 in the methylation of mRNA.

    • Lukas Trixl
    •  & Alexandra Lusser
  • Article |

    Takagi and colleagues report the crystal structure of human Wnt3 in complex with the mouse Frizzled 8 Cys-rich domain, a structural model of the Wnt–Frizzled–LRP6 ternary complex and engineered tagged versions of Wnt3a that retain biological function.

    • Hidenori Hirai
    • , Kyoko Matoba
    • , Emiko Mihara
    • , Takao Arimori
    •  & Junichi Takagi
  • News & Views |

    In the ribosome-associated quality control (RQC) pathway, stalled ribosomes are ubiquitinated and dissociated into subunits. The nascent protein chain associated with the 60S ribosomal subunit is ubiquitinated by the E3 ligase Listerin (Ltn1) and is released from tRNA by ANKZF1 (Vms1) for proteasomal degradation. Shao and colleagues now report that ANKZF1 (Vms1)-cleaved tRNAs are recycled via a two-step process that requires the removal of a terminal 2′,3′-cyclic phosphate and the addition of CCA by TRNT1.

    • Toshifumi Inada
  • Article |

    During ribosome-associated quality control (RQC), ANKZF1 severs polypeptidyl-tRNAs on RQC complexes by cleaving the terminal 3′CCA nucleotides, which leads to tRNA fragments that are ‘quality checked’ and recycled in the cytosol.

    • Matthew C. J. Yip
    • , Alexander F. A. Keszei
    • , Qing Feng
    • , Vincent Chu
    • , Michael J. McKenna
    •  & Sichen Shao
  • News & Views |

    Ribonucleotides that are misincorporated into DNA during replication are removed by topoisomerase 1, which generates 3′-terminal adducts that are not amenable to DNA repair and thus compromise genome stability. A recent report by Li et al. reveals that Apn2/APE2 resolves such blocked 3′ termini, thereby suppressing topoisomerase 1–induced mutations at ribonucleotide monophosphate sites within the genome.

    • Shan Yan
  • Article |

    Doudna and colleagues determine the mechanisms used by type V anti-CRISPR proteins. AcrVA1 is a multiple-turnover inhibitor that triggers cleavage of the Cas12a-bound guide RNA, while AcrVA4 and AcrVA5 inhibit recognition of dsDNA.

    • Gavin J. Knott
    • , Brittney W. Thornton
    • , Marco J. Lobba
    • , Jun-Jie Liu
    • , Basem Al-Shayeb
    • , Kyle E. Watters
    •  & Jennifer A. Doudna
  • News & Views |

    Bacteriophage-encoded anti-CRISPR (Acr) proteins were previously thought to inhibit CRISPR-mediated immunity by acting as physical barriers against the binding or cleavage of DNA. Two new studies report that recently discovered type V Acr proteins use enzymatic activities to shut down the Cas12a endonuclease, providing a multi-turnover ‘off switch’ for CRISPR-based immunity and technology.

    • Shravanti K. Suresh
    • , Karthik Murugan
    •  & Dipali G. Sashital
  • Article |

    Zhiwei Huang and colleagues report structural and biochemical data showing that the anti-CRISPR protein AcrVA5 functions as an acetyltransferase, modifying MbCas12a at Lys635, a residue required for PAM recognition. Acetylation of Lys635 creates a steric clash that prevents binding of target DNA.

    • Liyong Dong
    • , Xiaoyu Guan
    • , Ningning Li
    • , Fan Zhang
    • , Yuwei Zhu
    • , Kuan Ren
    • , Ling Yu
    • , Fengxia Zhou
    • , Zhifu Han
    • , Ning Gao
    •  & Zhiwei Huang
  • News & Views |

    RNAs perform diverse cellular functions that are mediated at least in part by their structure. However, how RNA structure changes throughout the RNA lifecycle and how these changes affect RNA function remain incompletely understood. A detailed in vivo characterization of RNA structure in various cellular subcompartments now provides insights into how RNA structural changes influence translation, RNA decay, protein binding and RNA modification.

    • Angela M Yu
    •  & Julius B. Lucks
  • Article |

    PICH and Topoisomerase 3a together introduce positive supercoiling into DNA, which could aid efficient sister-chromatid disjunction during mitosis.

    • Anna H. Bizard
    • , Jean-Francois Allemand
    • , Tue Hassenkam
    • , Manikandan Paramasivam
    • , Kata Sarlós
    • , Manika Indrajit Singh
    •  & Ian D. Hickson
  • News & Views |

    Intertwining of DNA molecules frequently results in the formation of ‘ultrafine bridges’ between sister chromatids that need to be resolved during segregation of the chromatids into daughter cells. Although it has been established that these DNA bridges are coated by the helicase PICH, it has remained unknown how PICH assists in their resolution. A study now reveals that PICH directs the formation of positive DNA supercoiling in the presence of type I topoisomerases to promote the subsequent disentanglement of these DNA helices by type II topoisomerases. Remarkably, PICH might be able to reconfigure DNA topology by extruding loops of DNA while it moves along the double helix.

    • Shveta Bisht
    •  & Christian H. Haering
  • News & Views |

    Chromatin organization in the nucleus plays an important role in cell-type-specific gene expression. A new study reports reconstruction of the 3D genome in single sensory neurons and provides insights into the regulation of genes encoding odorant receptors.

    • Lúcia M. Armelin-Correa
    •  & Bettina Malnic
  • Article |

    Structural and biochemical data suggest that the essential autophagy protein Atg2 acts as a lipid-transfer protein that supplies phospholipids from the source organelle (especially the ER) to the isolation membranes (IMs) for autophagosome formation.

    • Takuo Osawa
    • , Tetsuya Kotani
    • , Tatsuya Kawaoka
    • , Eri Hirata
    • , Kuninori Suzuki
    • , Hitoshi Nakatogawa
    • , Yoshinori Ohsumi
    •  & Nobuo N. Noda
  • Article |

    ATG12 and ATG5 are covalently conjugated during autophagy. Exceptions are now uncovered: in Plasmodium and Toxoplasma species and in yeast Komagataella phaffii (previously Pichia pastoris), ATG12 and ATG5 form a non-covalent yet functional complex.

    • Yu Pang
    • , Hayashi Yamamoto
    • , Hirokazu Sakamoto
    • , Masahide Oku
    • , Joe Kimanthi Mutungi
    • , Mayurbhai Himatbhai Sahani
    • , Yoshitaka Kurikawa
    • , Kiyoshi Kita
    • , Nobuo N. Noda
    • , Yasuyoshi Sakai
    • , Honglin Jia
    •  & Noboru Mizushima
  • News & Views |

    Ubiquitin and ubiquitin-like proteins (UBLs) are essential regulators of a multitude of cellular processes, including autophagy. It is known that these proteins relay their effects by covalently modifying their substrate molecules. As an exception to this norm, Pang et al. report a novel phenomenon in which the UBL ATG12 interacts with its substrate ATG5 in a non-covalent fashion to promote autophagy in apicomplexan parasites and some yeasts.

    • Varnesh Tiku
    •  & Ivan Dikic
  • Article |

    The cryo-EM structure of the Saccharomyces cerevisiae 80S ribosome–Xrn1 nuclease complex reveals how the conserved core of Xrn1 allows binding at the mRNA exit channel of the ribosome, ensuring efficient degradation of mRNA after the final round of translation.

    • Petr Tesina
    • , Elisabeth Heckel
    • , Jingdong Cheng
    • , Micheline Fromont-Racine
    • , Robert Buschauer
    • , Lukas Kater
    • , Birgitta Beatrix
    • , Otto Berninghausen
    • , Alain Jacquier
    • , Thomas Becker
    •  & Roland Beckmann
  • Resource |

    Structure maps of RNAs localized to chromatin, nucleoplasm and cytoplasm provide a rich resource with which to investigate the interplay of RNA structure, RNA–protein interactions and RNA modifications.

    • Lei Sun
    • , Furqan M. Fazal
    • , Pan Li
    • , James P. Broughton
    • , Byron Lee
    • , Lei Tang
    • , Wenze Huang
    • , Eric T. Kool
    • , Howard Y. Chang
    •  & Qiangfeng Cliff Zhang
  • Article |

    After acute agonist stimulation, phase-separated complexes form at estrogen-receptor-bound enhancer sites and coalesce into condensates with cooperative enhancer activity. Chronic stimulation causes the condensates to mature into a less dynamic, gel-like state.

    • Sreejith J. Nair
    • , Lu Yang
    • , Dario Meluzzi
    • , Soohwan Oh
    • , Feng Yang
    • , Meyer J. Friedman
    • , Susan Wang
    • , Tom Suter
    • , Ibraheem Alshareedah
    • , Amir Gamliel
    • , Qi Ma
    • , Jie Zhang
    • , Yiren Hu
    • , Yuliang Tan
    • , Kenneth A. Ohgi
    • , Ranveer Singh Jayani
    • , Priya R. Banerjee
    • , Aneel K. Aggarwal
    •  & Michael G. Rosenfeld
  • News & Views |

    Last year, several studies reported that proteins form biomolecular condensates at gene enhancers. Nair et al. now show that these condensates undergo physical changes over time, which affects their nuclear localization and the transcriptional output of their target genes.

    • Sina Wittmann
    •  & Simon Alberti
  • Article |

    The crystal structure of a broadly neutralizing monoclonal antibody against Ebola virus glycoprotein isolated from a human survivor allows the engineering of variant antibodies with expanded activity and has implications for vaccine design.

    • Brandyn R. West
    • , Anna Z. Wec
    • , Crystal L. Moyer
    • , Marnie L. Fusco
    • , Philipp A. Ilinykh
    • , Kai Huang
    • , Ariel S. Wirchnianski
    • , Rebekah M. James
    • , Andrew S. Herbert
    • , Sean Hui
    • , Eileen Goodwin
    • , Katie A. Howell
    • , Shweta Kailasan
    • , M. Javad Aman
    • , Laura M. Walker
    • , John M. Dye
    • , Alexander Bukreyev
    • , Kartik Chandran
    •  & Erica Ollmann Saphire
  • Article |

    Two evolutionarily distant SMC–kleisin complexes are shown to contain a bendable coiled-coil discontinuity near the middle of their arms, which permits a folded conformation with potential implications for DNA loading and translocation.

    • Frank Bürmann
    • , Byung-Gil Lee
    • , Thane Than
    • , Ludwig Sinn
    • , Francis J O’Reilly
    • , Stanislau Yatskevich
    • , Juri Rappsilber
    • , Bin Hu
    • , Kim Nasmyth
    •  & Jan Löwe
  • Article |

    Histone variant macroH2A1.2 and chromatin remodeler ATRX act jointly to maintain telomere integrity under conditions of acute replication stress in ALT-positive cancer cells.

    • Jeongkyu Kim
    • , Chongkui Sun
    • , Andy D. Tran
    • , Pei-Ju Chin
    • , Penelope D. Ruiz
    • , Kun Wang
    • , Richard J. Gibbons
    • , Matthew J. Gamble
    • , Yie Liu
    •  & Philipp Oberdoerffer
  • Article |

    In vivo and in vitro protein-RNA interaction maps identify an RNA-binding patch within the allosteric regulatory site of PRC2 that explains how RNA-mediated inhibition of PRC2 is relieved by allosteric activation.

    • Qi Zhang
    • , Nicholas J. McKenzie
    • , Robert Warneford-Thomson
    • , Emma H. Gail
    • , Sarena F. Flanigan
    • , Brady M. Owen
    • , Richard Lauman
    • , Vitalina Levina
    • , Benjamin A. Garcia
    • , Ralf B. Schittenhelm
    • , Roberto Bonasio
    •  & Chen Davidovich
  • Article |

    Mechanical distortion of DNA structure induces off-target binding and cleavage by SpyCas9 at sites with up to ten mismatches, a potential mechanism that exposes cryptic off-target sites in cells during transcription or replication.

    • Matthew D. Newton
    • , Benjamin J. Taylor
    • , Rosalie P. C. Driessen
    • , Leonie Roos
    • , Nevena Cvetesic
    • , Shenaz Allyjaun
    • , Boris Lenhard
    • , Maria Emanuela Cuomo
    •  & David S. Rueda
  • Article |

    Comparative Hi-C analysis of synchronized mouse spermatocyte populations reveals dynamic changes in chromosome organization during meiotic prophase that permit homolog pairing while sustaining gene expression.

    • Lucas Patel
    • , Rhea Kang
    • , Scott C. Rosenberg
    • , Yunjiang Qiu
    • , Ramya Raviram
    • , Sora Chee
    • , Rong Hu
    • , Bing Ren
    • , Francesca Cole
    •  & Kevin D. Corbett
  • Article |

    Structures of human 5-HT2AR in complex with several drugs reveal a side-extended cavity that is unique for this receptor, while molecular docking suggests that a highly 5-HT2AR-selective antagonist binds residues within this cavity.

    • Kanako Terakado Kimura
    • , Hidetsugu Asada
    • , Asuka Inoue
    • , Francois Marie Ngako Kadji
    • , Dohyun Im
    • , Chihiro Mori
    • , Takatoshi Arakawa
    • , Kunio Hirata
    • , Yayoi Nomura
    • , Norimichi Nomura
    • , Junken Aoki
    • , So Iwata
    •  & Tatsuro Shimamura
  • Article |

    A combination of bulk and single-molecule fluorescence analysis reveals the choreography of binding and rearrangement of individual DNA-binding domains of RPA during homologous recombination.

    • Nilisha Pokhrel
    • , Colleen C. Caldwell
    • , Elliot I. Corless
    • , Emma A. Tillison
    • , Joseph Tibbs
    • , Nina Jocic
    • , S. M. Ali Tabei
    • , Marc S. Wold
    • , Maria Spies
    •  & Edwin Antony
  • News & Views |

    Autophagy is a highly contextual modulator of tumorigenesis. A new study shows that autophagy can serve as a tumor suppressor to mediate cell death at replicative crisis.

    • Masashi Narita
  • Article |

    Assembly of proteasome subunits Rpt1 and Rpt2 is shown to occur co-translationally. Ribosomal pausing facilitates the incorporation of nascent Rpt1 and Rpt2 into Not-containing particles and their subsequent association with each other.

    • Olesya O. Panasenko
    • , Syam Prakash Somasekharan
    • , Zoltan Villanyi
    • , Marina Zagatti
    • , Fedor Bezrukov
    • , Ravish Rashpa
    • , Julien Cornut
    • , Jawad Iqbal
    • , Marion Longis
    • , Sarah H. Carl
    • , Cohue Peña
    • , Vikram G. Panse
    •  & Martine A. Collart
  • News & Views |

    Structural information on the respiratory supercomplex III2IV2 from budding yeast and from Mycobacterium smegmatis has become available, with cryo-EM work from four different groups.

    • Joana S. Sousa
    •  & Janet Vonck