Featured
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Letter |
Genome–lamina interactions are established de novo in the early mouse embryo
Spatial genome organization into lamina-associated domains is first established in the mouse zygote immediately after fertilization without inheritance from the maternal germline—with the paternal and maternal pronucleus exhibiting different organization, which subsequently converges prior to implantation of the embryo.
- Máté Borsos
- , Sara M. Perricone
- & Jop Kind
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Letter |
Late steps in bacterial translation initiation visualized using time-resolved cryo-EM
A time-resolved cryo-electron microscopy approach is used to visualize, at near-atomic resolution and on a sub-second timescale, short-lived intermediate states of a fundamental biomolecular reaction.
- Sandip Kaledhonkar
- , Ziao Fu
- & Joachim Frank
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News & Views |
Construction of an Escherichia coli genome with fewer codons sets records
The biggest synthetic genome so far has been made, with a smaller set of amino-acid-encoding codons than usual — raising the prospect of encoding proteins that contain unnatural amino-acid residues.
- Benjamin A. Blount
- & Tom Ellis
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Review Article |
Transcription factors and 3D genome conformation in cell-fate decisions
Three-dimensional genome architecture has important roles in the regulation of gene expression and is therefore a key determinant of cell identity in normal development and in disease states.
- Ralph Stadhouders
- , Guillaume J. Filion
- & Thomas Graf
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Article |
Total synthesis of Escherichia coli with a recoded genome
High-fidelity convergent total synthesis is used to produce
Escherichia coli with a 61-codon synthetic genome that uses 59 codons to encode all of the canonical amino acids.- Julius Fredens
- , Kaihang Wang
- & Jason W. Chin
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Letter |
Epigenetic evolution and lineage histories of chronic lymphocytic leukaemia
A single-cell approach is used to follow the heritable stochastic changes to DNA methylation that occur in primary chronic lymphocytic leukaemia and healthy B cells, allowing the tracing of cell lineage histories and evolution during treatment with ibrutinib.
- Federico Gaiti
- , Ronan Chaligne
- & Dan A. Landau
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Letter |
Transcriptional cofactors display specificity for distinct types of core promoters
A screen of 23 transcriptional cofactors for their ability to activate 72,000 candidate core promoters in Drosophila melanogaster identified distinct compatibility groups, providing insight into mechanisms that underlie the selective activation of transcriptional programs.
- Vanja Haberle
- , Cosmas D. Arnold
- & Alexander Stark
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Research Highlight |
Cells ‘hear’ messages with help from shape-shifting molecules
A receptor on cells has two forms, each associated with a different type of messaging.
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Letter |
Sensory experience remodels genome architecture in neural circuit to drive motor learning
The authors identify a role for genome architecture reorganization in anterior dorsal cerebellar vermis granule neurons in learning a conditioned startle paradigm in mice.
- Tomoko Yamada
- , Yue Yang
- & Azad Bonni
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Letter |
MicroRNA therapy stimulates uncontrolled cardiac repair after myocardial infarction in pigs
MicroRNAs delivered by adeno-associated viral vectors improve global and regional contractility, increase muscle mass and reduce scar size in a porcine model of myocardial infarction.
- Khatia Gabisonia
- , Giulia Prosdocimo
- & Mauro Giacca
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Technology Feature |
The new techniques revealing the varied shapes of chromatin
Researchers are realizing that the DNA–protein complex doesn’t just have one form but many.
- Jeffrey M. Perkel
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Letter |
Arabidopsis FLL2 promotes liquid–liquid phase separation of polyadenylation complexes
A genetic screen for factors required by the Arabidopsis RNA-binding protein FCA identifies FLL2 as necessary in the formation of FCA nuclear bodies, and thus a role for FLL2 in liquid–liquid phase separation.
- Xiaofeng Fang
- , Liang Wang
- & Caroline Dean
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Letter |
Mammalian ISWI and SWI/SNF selectively mediate binding of distinct transcription factors
Genetic deletion of mammalian chromatin remodelling complexes reveals that ISWI and SWI/SNF are required for binding of specific transcription factors and that ISWI regulates nucleosome positioning and nuclear organization in stem cells.
- Darko Barisic
- , Michael B. Stadler
- & Dirk Schübeler
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Letter |
Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors
CRISPR DNA base editors induce transcriptome-wide off-target RNA editing, which can be reduced by using engineered variants that retain on-target DNA editing activities.
- Julian Grünewald
- , Ronghao Zhou
- & J. Keith Joung
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Obituary |
Sydney Brenner (1927-2019)
Mischievous steward of molecular biology’s golden age.
- Errol Friedberg
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Letter |
p38γ is essential for cell cycle progression and liver tumorigenesis
The stress-activated kinase p38γ has a role in regulating entry into the cell cycle; in the liver, it can induce cellular proliferation during regeneration and promote the development of hepatocellular carcinoma.
- Antonia Tomás-Loba
- , Elisa Manieri
- & Guadalupe Sabio
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Article |
Nitrosative stress drives heart failure with preserved ejection fraction
iNOS-driven dysregulation of the IRE1α–XBP1 pathway leads to cardiomyocyte dysfunction in mice and recapitulates the systemic and cardiovascular features of human heart failure with preserved ejection fraction.
- Gabriele G. Schiattarella
- , Francisco Altamirano
- & Joseph A. Hill
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News & Views |
Genetic paradox explained by nonsense
Gene mutations that truncate the encoded protein can trigger the expression of related genes. The discovery of this compensatory response changes how we think about genetic studies in humans and model organisms.
- Miles F. Wilkinson
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Letter |
PTC-bearing mRNA elicits a genetic compensation response via Upf3a and COMPASS components
mRNA that contains a premature termination codon (PTC) triggers a genetic compensation response that involves both transcription of its homologous genes and degradation of the mutated transcript by the nonsense-mediated decay pathway.
- Zhipeng Ma
- , Peipei Zhu
- & Jun Chen
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Article |
Genetic compensation triggered by mutant mRNA degradation
Transcriptional adaptation, a genetic compensation process by which organisms respond to mutations by upregulating related genes, is triggered by mRNA decay and involves a sequence-dependent mechanism.
- Mohamed A. El-Brolosy
- , Zacharias Kontarakis
- & Didier Y. R. Stainier
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News Feature |
Protein-slaying drugs could be the next blockbuster therapies
Researchers are hijacking the cell’s protein-disposal system in the fight against Alzheimer’s and intractable cancers.
- Megan Scudellari
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Letter |
Recruitment of BRCA1 limits MYCN-driven accumulation of stalled RNA polymerase
In human neuroblastoma tumours, MYCN is engaged in a USP11–BRCA1-dependent manner to suppress the accumulation of stalled RNAPII and induces both the activation and repression of genes.
- Steffi Herold
- , Jacqueline Kalb
- & Martin Eilers
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Analysis |
The expanding landscape of ‘oncohistone’ mutations in human cancers
The characterization of missense histone mutations that occur across several cancer types provides insight into the potential role of these mutations in altering chromatin structure and potentially contributing to tumour development.
- Benjamin A. Nacev
- , Lijuan Feng
- & C. David Allis
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Article |
Visualizing DNA folding and RNA in embryos at single-cell resolution
Optical reconstruction of chromatin architecture and multiplex RNA labelling traces the DNA path in single cells and its relationship to transcription.
- Leslie J. Mateo
- , Sedona E. Murphy
- & Alistair N. Boettiger
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News & Views |
Modification of histone proteins by serotonin in the nucleus
The function of histone proteins can be modified through addition or removal of certain chemical groups. The addition of a serotonin molecule is a newly found histone modification that could influence gene expression.
- Marlene Cervantes
- & Paolo Sassone-Corsi
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Letter |
Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally
METTL14 recognizes the trimethyl mark on lysine 36 of histone H3 that directs m6A modifications co-transcriptionally.
- Huilin Huang
- , Hengyou Weng
- & Jianjun Chen
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Letter |
Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3
In serotonin-rich tissues, tissue transglutaminase 2 is able to attach serotonin to a glutamine residue in histone H3; this modification mediates permissive gene expression in these tissues.
- Lorna A. Farrelly
- , Robert E. Thompson
- & Ian Maze
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Letter |
Mechanism of DNA translocation underlying chromatin remodelling by Snf2
Cryo-EM structures of yeast Snf2 bound to the nucleosome in the presence of ADP or an ATP analogue reveal that Snf2 binding leads to distortion of the DNA, and a two-step mechanism underlying chromatin remodelling by Snf2 is proposed.
- Meijing Li
- , Xian Xia
- & Zhucheng Chen
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Letter |
TRAIP is a master regulator of DNA interstrand crosslink repair
The E3 ubiquitin ligase TRAIP governs the choice between the NEIL3 or the Fanconi anaemia pathway for the repair of DNA interstrand crosslinks.
- R. Alex Wu
- , Daniel R. Semlow
- & Johannes C. Walter
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Toolbox |
The race for enzymatic DNA synthesis heats up
An alternative to chemical oligonucleotide synthesis inches closer to reality.
- Jeffrey M. Perkel
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News |
Four new DNA letters double life’s alphabet
Synthetic DNA seems to behave like the natural variety, suggesting that chemicals beyond nature’s four familiar bases could support life on Earth.
- Matthew Warren
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News & Views |
Unstable genomes promote inflammation
Faulty DNA replication can make genomes unstable. It now seems that, in mice, severe disruption of DNA replication triggers inflammation in the placenta, and female embryos are more sensitive to this than are male ones.
- Sarah Lambert
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Article |
A single-cell molecular map of mouse gastrulation and early organogenesis
Single-cell profiling is used to create a molecular-level atlas of cell differentiation trajectories during gastrulation and early organogenesis in the mouse.
- Blanca Pijuan-Sala
- , Jonathan A. Griffiths
- & Berthold Göttgens
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Letter |
Multiplex chromatin interactions with single-molecule precision
A strategy using droplet-based and barcode-linked sequencing captures multiplex chromatin interactions at single-molecule precision, and here provides topological insight into chromatin structures and transcription in Drosophila.
- Meizhen Zheng
- , Simon Zhongyuan Tian
- & Yijun Ruan
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News & Views |
Inhibition of ‘jumping genes’ promotes healthy ageing
DNA sequences called retrotransposons can copy themselves and reintegrate at new sites in the genome, causing damage. It now seems that inhibiting this process can prevent age-related health decline in mice.
- Bennett Childs
- & Jan van Deursen
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Article |
L1 drives IFN in senescent cells and promotes age-associated inflammation
During cellular senescence in human and mouse cells, L1 transposons become transcriptionally derepressed and trigger a type-1 interferon response, which contributes to age-associated inflammation and age-related phenotypes.
- Marco De Cecco
- , Takahiro Ito
- & John M. Sedivy
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Letter |
Anti-tumour immunity controlled through mRNA m6A methylation and YTHDF1 in dendritic cells
The m6A reader protein YTHDF1 suppresses the clearance of tumour cells by enhancing the translation of lysosomal proteases in dendritic cells and thereby suppressing tumour antigen presentation.
- Dali Han
- , Jun Liu
- & Chuan He
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Letter |
PKG1-modified TSC2 regulates mTORC1 activity to counter adverse cardiac stress
Phosphorylation of one of two adjacent serine residues in TSC2 is both required and sufficient for PKG1-mediated cardiac protection against pressure overload in mice; these serine residues provide a genetic tool for the bidirectional regulation of stress-stimulated mTORC1 activity.
- Mark J. Ranek
- , Kristen M. Kokkonen-Simon
- & David A. Kass
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Letter |
Autophagic cell death restricts chromosomal instability during replicative crisis
Cell death during replicative crisis involves autophagy induced by telomere dysfunction.
- Joe Nassour
- , Robert Radford
- & Jan Karlseder
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News & Views |
Intron RNA sequences help yeast cells to survive starvation
Intron sequences are removed from newly synthesized RNA and usually rapidly degraded. However, it now seems that introns have a surprising role — helping yeast cells survive when nutrients are scarce.
- Samantha R. Edwards
- & Tracy L. Johnson
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Article |
Excised linear introns regulate growth in yeast
A set of 34 excised introns in Saccharomyces cerevisiae, characterized by having a short distance between the lariat branch point and the 3′ splice site, have a biological function within the TOR growth-signalling network.
- Jeffrey T. Morgan
- , Gerald R. Fink
- & David P. Bartel
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Article |
Introns are mediators of cell response to starvation
Transcriptomic and genetic analyses of a deletion set of all known introns in genes of the budding yeast Saccharomyces cerevisiae indicate that introns promote resistance to starvation.
- Julie Parenteau
- , Laurine Maignon
- & Sherif Abou Elela
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Research Highlight |
CRISPR adapted to respond to infected cells
Engineered tweaks to the popular gene-editing system allow it to fight viral infection.
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News & Views |
Protein modification fine-tunes the cell’s force producers
Identification of the enzyme that catalyses a site-specific modification of the protein actin reveals how this change modulates the function of the cell’s force-producing machinery.
- Pekka Lappalainen
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Letter |
Mobile PEAR transcription factors integrate positional cues to prime cambial growth
Radial growth in the roots of Arabidopsis, which is mediated by gene expression activated by the mobile PEAR1 and PEAR2 transcription factors, is initiated around protophloem-sieve-element cell files of procambial tissue.
- Shunsuke Miyashima
- , Pawel Roszak
- & Ykä Helariutta
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Letter |
FTSJ3 is an RNA 2′-O-methyltransferase recruited by HIV to avoid innate immune sensing
HIV-1 uses the host protein FTSJ3 to methylate its own genome, thereby evading detection by the innate immune system.
- Mathieu Ringeard
- , Virginie Marchand
- & Yamina Bennasser
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Letter |
Subcellular transcriptomes and proteomes of developing axon projections in the cerebral cortex
A subcellular sorting approach enables quantitative analysis of subtypes of growth cones in the brain, and reveals subcellular relationships between local mRNA and local proteomes in developing projection neurons.
- Alexandros Poulopoulos
- , Alexander J. Murphy
- & Jeffrey D. Macklis
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Article |
LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice
Specific interchromosomal contacts in olfactory sensory neurons form a super-enhancer that controls the expression of a single olfactory receptor in each neuron.
- Kevin Monahan
- , Adan Horta
- & Stavros Lomvardas
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Letter |
Structures of an RNA polymerase promoter melting intermediate elucidate DNA unwinding
Cryo-electron microscopy structures of bacterial RNAP–promoter DNA complexes, including structures of partially melted intermediates, suggest a universally conserved common mechanism for promoter DNA opening prior to gene expression.
- Hande Boyaci
- , James Chen
- & Elizabeth A. Campbell
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