Molecular biology

  • Article
    | Open Access

    The chromatin remodeler Chd1 mediates hypertranscription in embryonic stem (ES) cells and has been shown to associate with genes transcribed by RNA Polymerase (Pol) I and II. Here the authors provide mechanistic insights into this process and reveal that Chd1 is involved in protecting genome integrity at promoter regions by preventing DNA break accumulation.

    • Aydan Bulut-Karslioglu
    • , Hu Jin
    •  & Miguel Ramalho-Santos
  • Article
    | Open Access

    UNC5B is a Netrin-1 receptor expressed in endothelial cells that in the absence of ligand induces apoptosis. Here the authors identify an UNC5B splicing isoform that is insensitive to the pro-survival ligand Netrin-1 and is required for apoptosis-dependent blood vessel development.

    • Davide Pradella
    • , Gianluca Deflorian
    •  & Claudia Ghigna
  • Article
    | Open Access

    Embryos at the 2-cell (2C) stage are totipotent, and overexpression of Dux transcription factor convert embryonic stem cells (ESCs) to a 2C-like state. Here the authors show that DUX-mediated 2C-like reprogramming is associated with DNA damage at CTCF sites and CTCF depletion promotes 2Clike conversion.

    • Teresa Olbrich
    • , Maria Vega-Sendino
    •  & Sergio Ruiz
  • Article
    | Open Access

    Error-prone repair of DNA double-strand breaks have been implied to cause cancer-associated genome alterations, but the mechanism of their formation remains unclear. Here the authors find that DNA polymerase α primase plays part in tandem duplication formation at CRISPR/Cas9-induced complementary 3′ ssDNA protrusions.

    • Joost Schimmel
    • , Núria Muñoz-Subirana
    •  & Marcel Tijsterman
  • Article
    | Open Access

    Myocardial regeneration and proliferation of heart muscle cells is limited to a short period after birth early postnatal life, after which heart muscle cells can only grow in size and not in number. Here, the authors identified that the expression level of an endogenous microRNA cluster in heart muscle promotes the passage of the proliferative state to adult heart growth, and modulating the expression of this cluster can stimulate heart regeneration after myocardial infarction.

    • Andrea Raso
    • , Ellen Dirkx
    •  & Leon J. De Windt
  • Article
    | Open Access

    RPAP3 is a subunit of the R2TP complex, a co-chaperone of HSP90, with substrate proteins involved in transcription, ribosome biogenesis, DNA repair and cell growth. Here the authors report that deletion of Rpap3 abrogates cell proliferation and homeostasis in mouse intestine, partly through destabilization of PI3K-like kinases, while elevated RPAP3 levels in colorectal tumors are associated with poor prognosis.

    • Chloé Maurizy
    • , Claire Abeza
    •  & Bérengère Pradet-Balade
  • Article
    | Open Access

    Post-translational modifications are important regulators of NLRP3 inflammasome activity. Here the authors show that the E3 ligase TRIM28 can SUMOylate NLRP3, thereby limiting its proteasomal degradation and increasing NLRP3 inflammasome activity.

    • Ying Qin
    • , Qi Li
    •  & Wei Zhao
  • Article
    | Open Access

    The cyanophage S-2L incorporates 2-aminoadenine (Z) instead of adenine into its DNA, which still pairs with thymine forming a triple hydrogen bond. Here, the authors identify a third gene mazZ located between purZ and datZ that is required for 2-aminoadenine biosynthesis and determine the crystal structures of MazZ and PurZ. They further show that co-expression of these three genes in E.coli enables 2-aminoadenine incorporation into the bacterial genome.

    • Dariusz Czernecki
    • , Frédéric Bonhomme
    •  & Marc Delarue
  • Article
    | Open Access

    Ribosome biogenesis is crucially dependent on proper rRNA folding, a process assisted by chaperones. Here the authors reveal how Puf6 promotes correct rRNA folding at low temperature, a condition where mis-paired RNA folding intermediates frequently accumulate.

    • Stefan Gerhardy
    • , Michaela Oborská-Oplová
    •  & Vikram Govind Panse
  • Article
    | Open Access

    Translational frameshifting is a mechanism that expands the coding capabilities of mRNA. Here, structures of 70S ribosome complexes with GTPase elongation factor G (EF-G), a +1-frameshifting-prone mRNA and tRNAs reveal the cooperation between the ribosome and EF-G to induce +1 frameshifting during the translocation step.

    • Gabriel Demo
    • , Howard B. Gamper
    •  & Andrei A. Korostelev
  • Article
    | Open Access

    IWS1 regulates multiple steps in RNA metabolism, including RNA elongation and alternative RNA splicing. Here the authors show that AKT3 phosphorylates IWS1, which alters U2AF2 RNA splicing and promotes growth of lung adenocarcinomas via a Sororin/ERK-dependent pathway.

    • Georgios I. Laliotis
    • , Evangelia Chavdoula
    •  & Philip N. Tsichlis
  • Article
    | Open Access

    The polycomb repressive complex 2 (PRC2) is a histone methyltransferase regulating cell differentiation and identity. Here, the authors show that the vertebrate-specific PRC2 accessory subunit PALI1 facilitates substrate binding by the complex and elucidate the allosteric mechanism of PALI1- mediated PRC2 activation.

    • Qi Zhang
    • , Samuel C. Agius
    •  & Chen Davidovich
  • Article
    | Open Access

    PARG and ARH3 are the main hydrolases to reverse serine poly(ADP-ribosylation) yet their activities in the process differ. Here, the authors synthesise linear and branched poly(ADP-ribose) molecules, perform structure-function analysis and elucidate the mechanistic differences between PARG and ARH3.

    • Johannes Gregor Matthias Rack
    • , Qiang Liu
    •  & Ivan Ahel
  • Article
    | Open Access

    Cytokinetic ring constriction during cell division requires actin but curiously is independent of myosin in many organisms. Here, the authors show that anillin, a protein enriched in the contractile ring, is a non-motor actin crosslinker that generates contractile force in lieu of a molecular motor.

    • Ondřej Kučera
    • , Valerie Siahaan
    •  & Zdenek Lansky
  • Article
    | Open Access

    S-acylation is the post-translational covalent attachment of fatty acids (FA) onto cysteines. Nuskova et al. find that exposure of cells to different FAs affects which FA is used to S-acylate GNAI proteins, thereby altering GNAI function and EGFR pathway activation, linking metabolism to signaling.

    • Hana Nůsková
    • , Marina V. Serebryakova
    •  & Aurelio A. Teleman
  • Article
    | Open Access

    We know that most splicing reactions take place co-transcriptionally, but how the transcription machinery facilitate splicing of introns is unknown. Here the authors show that the 5′ splice site remains associated with the transcription machinery during intron synthesis through U1 snRNP, providing a basis for the rapid splicing reaction of introns.

    • Yodfat Leader
    • , Galit Lev Maor
    •  & Gil Ast
  • Article
    | Open Access

    Assembly of the mitoribosome requires assistance from numerous specialized factors. Here, structures of the human 39S late assembly intermediates identify several assembly factors which keep the 16S rRNA in immature conformations, and reveal deacylated tRNA in the ribosomal E-site, suggesting a role in 39S assembly.

    • Jingdong Cheng
    • , Otto Berninghausen
    •  & Roland Beckmann
  • Perspective
    | Open Access

    A key feature of living cells is the cell cycle. In this Perspective, the authors explore attempts to recreate this process and what is still required for an integrated synthetic cell cycle.

    • Lorenzo Olivi
    • , Mareike Berger
    •  & John van der Oost
  • Article
    | Open Access

    Chemical modulation of intron selection has emerged as a route for cancer therapy. Here, structures of the U2 snRNP’s SF3B module and of prespliceosome- both in complexes with splicing modulators- provide insight into the mechanisms of intron recognition and branch site inactivation.

    • Constantin Cretu
    • , Patricia Gee
    •  & Vladimir Pena
  • Article
    | Open Access

    Reactive oxygen species (ROS) are metabolic by-products which in excess can be toxic for hematopoietic stem and progenitor cells (HSPCs). Here the authors show that toxic ROS are transferred by expanding HSPCs to the zebrafish developmental niche via connexin Cx41.8, where Ifi30 promotes their detoxification.

    • Pietro Cacialli
    • , Christopher B. Mahony
    •  & Julien Y. Bertrand
  • Article
    | Open Access

    Here the authors decode how core promoter elements regulate rate limiting steps of transcription using quantitative live imaging, genetics and modeling in early Drosophila embryos. TATA-driven promoters require one rate-limiting step while INR promoters need an extra step associated with Pol II pausing.

    • Virginia L. Pimmett
    • , Matthieu Dejean
    •  & Mounia Lagha
  • Article
    | Open Access

    The ability of HIV to alternate between acute and latent forms is thought to rely on a transcriptional feedback loop where polymerase pausing is released by the viral protein Tat. Here, the authors show that viral genome transcription can occur in a burst-like stochastic manner in the absence of Tat.

    • Katjana Tantale
    • , Encar Garcia-Oliver
    •  & Edouard Bertrand
  • Article
    | Open Access

    Different factors protect cells from harmful R-loops, but the way these are formed is still unclear. Authors show here that R-loops form co-transcriptionally by different manners and cells possess specialized mechanisms to prevent them in each case, a major mechanism being independent of replication and another one being linked to replication.

    • Marta San Martin-Alonso
    • , María E. Soler-Oliva
    •  & Andrés Aguilera
  • Article
    | Open Access

    The Class 2 family of CRISPR nucleases named Cas12j, which shares only low sequence identity with other CRISPR nucleases was recently identified in the biggiephage clade of phages. Here, the authors present the cryo-EM structure of a functional Cas12j3−crRNA complex in the post-catalytic state and discuss Cas12j3 PAM recognition, hybrid stabilisation and the activation mechanism.

    • Arturo Carabias
    • , Anders Fuglsang
    •  & Guillermo Montoya
  • Article
    | Open Access

    Whether thyroid hormones affect gene expression via DNA methylation is not well known. Here the authors show that type 2 deiodinase (D2) converts T4 to produce T3, which prevents DNA methylation of discrete areas in the neonatal liver. In the absence of D2, DNA methylation occurs and is associated with reduced chromatin accessibility in promoters and enhancers and affects gene expression.

    • Tatiana L. Fonseca
    • , Tzintzuni Garcia
    •  & Antonio C. Bianco
  • Article
    | Open Access

    Globin loci harbor genes that are expressed embryonically and silenced postnatally. Here the authors show that zeta-globin silencing depends upon selective hypoacetylation of its TAD subdomain, which blocks its interaction with the alpha-globin super-enhancer, and zeta-globin can be reactivated by acetylation.

    • Andrew J. King
    • , Duantida Songdej
    •  & Christian Babbs
  • Article
    | Open Access

    The small RNA RepG modulates expression of chemotaxis receptor TlpB in Helicobacter pylori by targeting a length-variable G-repeat in the tlpB mRNA. Here, Pernitzsch et al. show that RepG also gradually controls lipopolysaccharide biosynthesis, antibiotic susceptibility, and in-vivo colonization of the stomach, by regulating a gene that is co-transcribed with tlpB.

    • Sandy R. Pernitzsch
    • , Mona Alzheimer
    •  & Cynthia M. Sharma
  • Article
    | Open Access

    Spatial analysis of RNAseq data is important. Here the authors report a method for transcriptome profiling combined with photo-isolation chemistry to allow determination of expression profiles specifically from photo-irradiated regions of interest which they use in mouse brains and embryonic tissues.

    • Mizuki Honda
    • , Shinya Oki
    •  & Yasuyuki Ohkawa
  • Review Article
    | Open Access

    Mosquito-borne diseases pose significant global health burdens. In this review, the authors explore Wolbachia and genome engineering approaches to mosquito-borne disease population control.

    • Guan-Hong Wang
    • , Stephanie Gamez
    •  & Omar S. Akbari
  • Article
    | Open Access

    Glucocorticoids (GC) are reported to block cancer cell proliferation, but the mode of action is unclear. Here the authors show that glucocorticoid receptor activation induces cancer cell dormancy in lung cancer by regulating CDKN1C expression through a distal enhancer, and these dormant cells are addicted to IGF-1R signalling pathway.

    • Stefan Prekovic
    • , Karianne Schuurman
    •  & Wilbert Zwart
  • Article
    | Open Access

    Break-induced replication (BIR), a subtype of HR, is a mutagenic mechanism that leads to chromosome rearrangements. Here the authors reveal insights into the role of Abraxas in limiting excessive DNA end resection, R-loop accumulation and cells undergoing BIR-dependent mitotic DNA synthesis.

    • Xiao Wu
    •  & Bin Wang
  • Article
    | Open Access

    Memory T cells are particularly reliant on fatty acid oxidation as a source of energy. Here the authors show this reliance is controlled by AMPK sensing of glucose deprivation that triggers SENP1-Sirt3 signalling, driving fatty acid oxidation and memory differentiation in T cells via deacetylation of YME1L1 to induce mitochondrial fusion.

    • Jianli He
    • , Xun Shangguan
    •  & Jinke Cheng