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Article
| Open AccessConserved and divergent gene regulatory programs of the mammalian neocortex
A single-cell multiomics analysis of over 200,000 cells of the primary motor cortex of human, macaque, marmoset and mouse shows that divergence of transcription factor expression corresponds to species-specific epigenome landscapes, and conserved and divergent gene regulatory features are reflected in the evolution of the three-dimensional genome.
- Nathan R. Zemke
- , Ethan J. Armand
- & Bing Ren
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Article
| Open AccessSingle-cell analysis of chromatin accessibility in the adult mouse brain
An atlas of candidate cis-regulatory DNA elements (cCREs) in the adult mouse brain unravels the transcriptional regulatory programs that drive the heterogeneity and complexity of brain structure and function.
- Songpeng Zu
- , Yang Eric Li
- & Bing Ren
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Article
| Open AccessN1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting
A study demonstrates that nucleotide modifications in mRNA-based therapeutics can lead to +1 ribosomal frameshifting during translation, yielding products that can trigger immune responses.
- Thomas E. Mulroney
- , Tuija Pöyry
- & Anne E. Willis
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Article
| Open AccessTAF15 amyloid filaments in frontotemporal lobar degeneration
Cryogenic electron microscopy structures of amyloid filaments extracted from patient brains reveal that the protein TAF15 forms filaments that characterize certain cases of frontotemporal lobar degeneration.
- Stephan Tetter
- , Diana Arseni
- & Benjamin Ryskeldi-Falcon
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News & Views |
An immune-cell transcription factor tethers DNA together
A transcription factor in immune cells forms an unexpectedly ladder-like complex with two DNA molecules, allowing the expression of genes that these cells need to suppress harmful immune responses.
- Zhi Liu
- & Ye Zheng
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Article
| Open AccessIdentification of constrained sequence elements across 239 primate genomes
Whole-genome alignment of 239 primate species reveals noncoding regulatory elements that are under selective constraint in primates but not in other placental mammals, that are enriched for variants that affect human gene expression and complex traits in diseases.
- Lukas F. K. Kuderna
- , Jacob C. Ulirsch
- & Kyle Kai-How Farh
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Article |
mRNA reading frame maintenance during eukaryotic ribosome translocation
The accuracy of eukaryotic ribosome translocation relies on eukaryote-specific elements of the 80S ribosome, elongation factor 2 and transfer RNAs, all of which contribute to the maintenance of the messenger RNA reading frame.
- Nemanja Milicevic
- , Lasse Jenner
- & Gulnara Yusupova
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Article |
Stepwise requirements for polymerases δ and θ in theta-mediated end joining
Polymerase delta is required for multiple steps in polymerase theta-dependent repair of chromosome breaks, a pathway targeted in cancer therapy.
- Susanna Stroik
- , Juan Carvajal-Garcia
- & Dale A. Ramsden
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Article |
Asymmetric distribution of parental H3K9me3 in S phase silences L1 elements
The epigenetic modification H3K9me3 is asymmetrically partitioned at long interspersed nuclear element retrotransposons for their silencing in S phase, a newly discovered mechanism that is mediated by the HUSH complex and the DNA polymerase Pol ε.
- Zhiming Li
- , Shoufu Duan
- & Zhiguo Zhang
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Article |
TNRC18 engages H3K9me3 to mediate silencing of endogenous retrotransposons
Trinucleotide-repeat-containing 18 (TNRC18), which has poorly understood functions, is now identified as an H3K9me3-specific reader that silences endogenous retroviruses.
- Shuai Zhao
- , Jiuwei Lu
- & Gang Greg Wang
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News & Views |
Viruses use RNA decoys to thwart CRISPR defences
Bacteria and archaea are microorganisms that often use RNA-guided defences called CRISPR to destroy the genomes of viruses that infect them. It now emerges that viruses make RNAs that act as mimics to divert such defences.
- Carolyn Kraus
- & Erik J. Sontheimer
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Article
| Open AccessChromatin compartmentalization regulates the response to DNA damage
After the production of double-stranded breaks in mammalian cells, ATM drives the formation of the D compartment, which regulates DNA damage-responsive genes, through the clustering of damaged topologically associating domains, with a mechanism that is consistent with polymer–polymer phase separation.
- Coline Arnould
- , Vincent Rocher
- & Gaëlle Legube
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Article
| Open AccessBacteriophages suppress CRISPR–Cas immunity using RNA-based anti-CRISPRs
In response to bacterial CRISPR–Cas immunity, phages and plasmids have evolved small non-coding RNA anti-CRISPRs, known as Racrs, that sequester Cas proteins in abberrant complexes and thereby inhibit immunity.
- Sarah Camara-Wilpert
- , David Mayo-Muñoz
- & Rafael Pinilla-Redondo
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News |
Anti-ageing molecule boosts fertility in ageing mice
‘Undeniably groundbreaking’ work shows that declining egg quality in older mice can be reversed with a dietary supplement.
- Gemma Conroy
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Perspective |
The status of the human gene catalogue
Although the catalogue of human protein-coding genes is nearing completion, the number of non-coding RNA genes remains highly uncertain, and for all genes much work remains to be done to understand their functions.
- Paulo Amaral
- , Silvia Carbonell-Sala
- & Steven L. Salzberg
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Article
| Open AccessLarge-scale plasma proteomics comparisons through genetics and disease associations
Comparisons of phenotypic and genetic association with protein levels from Icelandic and UK Biobank cohorts show that using multiple analysis platforms and stratifying populations by ancestry improves the detection of associations and allows the refinement of their location within the genome.
- Grimur Hjorleifsson Eldjarn
- , Egil Ferkingstad
- & Kari Stefansson
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Article
| Open AccessPlasma proteomic associations with genetics and health in the UK Biobank
The Pharma Proteomics Project generates the largest open-access plasma proteomics dataset to date, offering insights into trans protein quantitative trait loci across multiple biological domains, and highlighting genetic influences on ligand–receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks.
- Benjamin B. Sun
- , Joshua Chiou
- & Christopher D. Whelan
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News & Views |
Master regulator of a mosquito X chromosome discovered
In organisms with X and Y chromosomes, gene expression must be equalized between the sexes. A protein that causes upregulation of gene expression of the X chromosome in male mosquitoes has been discovered.
- Maggie P. Lauria Sneideman
- & Victoria H. Meller
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Article
| Open AccessThe sex-specific factor SOA controls dosage compensation in Anopheles mosquitoes
A newly identified gene, sex chromosome activation (SOA), is a master regulator of dosage compensation in Anopheles gambiae.
- Agata Izabela Kalita
- , Eric Marois
- & Claudia Isabelle Keller Valsecchi
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Article |
Transposon-encoded nucleases use guide RNAs to promote their selfish spread
TnpB and IscB nucleases use transposon-encoded guide RNAs to target genomic sequences for cleavage, thereby favouring copying and spreading of transposable elements.
- Chance Meers
- , Hoang C. Le
- & Samuel H. Sternberg
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Article
| Open AccessInhibition of fatty acid oxidation enables heart regeneration in adult mice
Inhibition of the fatty acid oxidation metabolic pathway through inactivation of Cpt1b enhances cardiomyocyte survival and proliferation and allows heart regeneration in adult mice.
- Xiang Li
- , Fan Wu
- & Thomas Braun
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Article
| Open AccessSpatial atlas of the mouse central nervous system at molecular resolution
In situ spatial transcriptomic analysis of more than 1 million cells are used to create a 200-nm-resolution spatial molecular atlas of the adult mouse central nervous system and identify previously unknown tissue architectures.
- Hailing Shi
- , Yichun He
- & Xiao Wang
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Article
| Open AccesspiRNA processing by a trimeric Schlafen-domain nuclease
The endoribonuclease PUCH, a trimer of Schlafen-like-domain proteins, initiates piRNA processing in the nematode Caenorhabditis elegans through 5′-end piRNA precursor cleavage.
- Nadezda Podvalnaya
- , Alfred W. Bronkhorst
- & René F. Ketting
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Article |
Acetyl-methyllysine marks chromatin at active transcription start sites
Cellular lysine residues can be both methylated and acetylated on the same sidechain to form Nε-acetyl-Nε-methyllysine (Kacme), which is found on histone H4 across a range of species and across mammalian tissues and is associated with active chromatin.
- William J. Lu-Culligan
- , Leah J. Connor
- & Matthew D. Simon
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Article
| Open AccessTranscriptional linkage analysis with in vivo AAV-Perturb-seq
An in vivo single-cell CRISPR screening method identifies transcriptional phenotypes of 22q11.2 deletion syndrome associated with a broad dysregulation of a class of disease susceptibility genes that are important for RNA processing and synaptic function.
- Antonio J. Santinha
- , Esther Klingler
- & Randall J. Platt
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News Feature |
FedEx for your cells: this biological delivery service could treat disease
Researchers want to know why cells produce tiny packages called vesicles — and whether these bundles could be used for therapy.
- Alison Abbott
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News & Views |
Dynamic regulation of messenger RNA structure controls translation
During translation, messenger RNA guides protein production, and certain conditions can favour particular proteins. Helicase enzymes and mRNA structure control translation during defence responses in plants.
- Yizhu Lin
- & Stephen N. Floor
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Article
| Open AccessPolθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis
In mitosis, genome integrity is maintained by DNA polymerase theta-dependent repair of DNA double-strand breaks, which is regulated by Polo-like kinase 1 activity.
- Camille Gelot
- , Marton Tibor Kovacs
- & Raphael Ceccaldi
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Article
| Open AccessPervasive downstream RNA hairpins dynamically dictate start-codon selection
Double-stranded RNA structures downstream of start codons play a role in translation initiation by regulating start-codon selection in plant immune responses, and also contribute to translational reprogramming in mammalian systems.
- Yezi Xiang
- , Wenze Huang
- & Xinnian Dong
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Article
| Open AccessHigh-resolution landscape of an antibiotic binding site
A collection of RNA polymerase mutants spanning all possible substitutions of the rifampicin binding site is generated and characterized, increasing our understanding of antibiotic mechanisms and bacterial physiology.
- Kevin B. Yang
- , Maria Cameranesi
- & Evgeny Nudler
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Article |
The complete sequence of a human Y chromosome
We present the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference.
- Arang Rhie
- , Sergey Nurk
- & Adam M. Phillippy
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Article
| Open AccessEndothelial sensing of AHR ligands regulates intestinal homeostasis
Single-cell transcriptomics and in vivo challenge models establish a key role for the aryl hydrocarbon receptor in regulating the function of enteric endothelial cells in response to environmental cues.
- Benjamin G. Wiggins
- , Yi-Fang Wang
- & Chris Schiering
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Article
| Open AccessLong-molecule scars of backup DNA repair in BRCA1- and BRCA2-deficient cancers
Linked-read whole-genome sequencing reveals patterns of structural DNA variants that are specific to homologous recombination deficiency and can be used to distinguish between BRCA1- and BRCA2-deficient phenotypes.
- Jeremy Setton
- , Kevin Hadi
- & Marcin Imieliński
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Article
| Open AccessA viral ADP-ribosyltransferase attaches RNA chains to host proteins
Bacteriophage T4 uses an enzyme known as ADP-ribosyltransferase ModB to modify the translational apparatus of bacteria it infects, not only by ADP-ribosylating proteins, but also by attaching entire RNA chains in a process known as RNAylation.
- Maik Wolfram-Schauerte
- , Nadiia Pozhydaieva
- & Katharina Höfer
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Article
| Open AccessDirect observation of the conformational states of PIEZO1
The plasma membrane can expand the blades of the PIEZO1 ion channel, impacting channel activation.
- Eric M. Mulhall
- , Anant Gharpure
- & Ardem Patapoutian
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Article
| Open AccessR-loop-dependent promoter-proximal termination ensures genome stability
SOSS–INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability.
- Congling Xu
- , Chengyu Li
- & Fei Xavier Chen
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Article
| Open AccessTRIM5α restricts poxviruses and is antagonized by CypA and the viral protein C6
The well-characterized HIV restriction factor TRIM5α also restricts orthopoxviruses and is countered by the viral protein C6 and the proviral activity of CypA, which in turn is antagonized by CsA and derivatives alisporivir and NIM811.
- Yiqi Zhao
- , Yongxu Lu
- & Geoffrey L. Smith
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Obituary |
Donald D. Brown, groundbreaking embryologist (1931–2023)
Molecular biologist whose work on isolated genes helped launch the era of recombinant DNA and gene editing.
- Susan A. Gerbi
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Article
| Open AccessTDP-43 forms amyloid filaments with a distinct fold in type A FTLD-TDP
Cryo-electron microscopy structures and mass spectrometry analyses show that TAR DNA-binding protein 43 (TDP-43) forms amyloid filaments with a distinct fold in type A frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) compared with TDP-43 filaments in type B FTLD-TDP and amyotrophic lateral sclerosis.
- Diana Arseni
- , Renren Chen
- & Benjamin Ryskeldi-Falcon
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Article
| Open AccessEinkorn genomics sheds light on history of the oldest domesticated wheat
Around 1% of the A subgenome of modern bread wheat (Triticum aestivum) originates from einkorn (Triticum monococcum), the first domesticated wheat species.
- Hanin Ibrahim Ahmed
- , Matthias Heuberger
- & Simon G. Krattinger
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News |
Experimental insulin implant uses electricity to control genes
Human cells that have been engineered to respond to an electrical current could be incorporated into future medical devices.
- Lilly Tozer
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Article |
Evolutionarily divergent mTOR remodels translatome for tissue regeneration
Rapid activation of protein synthesis in the axolotl highlights the unanticipated impact of a translatome on orchestrating the early steps of wound healing and provides a missing link in our understanding of vertebrate regenerative potential.
- Olena Zhulyn
- , Hannah D. Rosenblatt
- & Maria Barna
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News & Views |
Dynamics of protein droplets revealed by bridging multiple scales
Many biological processes rely on proteins that aggregate into droplets governed by dynamics that span myriad scales. A clever combination of spectroscopy and simulation offers a way to probe these diverse dynamics.
- Marina G. Guenza
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Article
| Open AccessDiverse modes of H3K36me3-guided nucleosomal deacetylation by Rpd3S
Structural and biochemical studies of the Saccharomyces cerevisiae Rpd3 small complex in free and H3K36me3 nucleosome-bound states reveal multiple nucleosome-binding modes and provide insights into mechanisms underlying epigenetic regulation by histone modification.
- Haipeng Guan
- , Pei Wang
- & Haitao Li
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News & Views |
Sleeping embryonic genomes are awoken by OBOX proteins
Activation of gene transcription is precisely regulated in early embryos. The identification of key transcription factors now shows how the transcription machinery is guided to the right place at the right time in mice.
- Edlyn Wu
- & Nadine L. Vastenhouw
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Article |
OBOX regulates mouse zygotic genome activation and early development
OBOX, PRD-like homeobox domain transcription factors (OBOX1–OBOX8), are key regulators of mouse zygotic genome activation and early embryogenesis.
- Shuyan Ji
- , Fengling Chen
- & Wei Xie
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Matters Arising
| Open AccessReply to: Cold induction of nuclear FRIGIDA condensation in Arabidopsis
- Pan Zhu
- & Caroline Dean
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Research Briefing |
Genetic ‘parasites’ hijack a DNA-repair pathway to form circular DNA and replicate
Retrotransposons are sequences of DNA in animal genomes that can replicate and reinsert themselves back into the genome. Experiments in flies and other model systems reveal that retrotransposons ‘hijack’ a DNA-repair pathway in host cells to produce circular DNA, enabling their replication and subsequent reinsertion into the genome.
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Matters Arising
| Open AccessCold induction of nuclear FRIGIDA condensation in Arabidopsis
- Zhicheng Zhang
- , Xiao Luo
- & Yuehui He
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