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Molecular hallmarks of heterochronic parabiosis at single-cell resolution
A transcriptomics study demonstrates cell-type-specific responses to differentially aged blood and shows young blood to have restorative and rejuvenating effects that may be invoked through enhanced mitochondrial function.
- Róbert Pálovics
- , Andreas Keller
- & Tony Wyss-Coray
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Article |
A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk
A method called vessel isolation and nuclei extraction for sequencing (VINE-seq) produces a molecular map of vascular and perivascular cell types in the human brain and reveals their contributions to Alzheimer’s disease risk.
- Andrew C. Yang
- , Ryan T. Vest
- & Tony Wyss-Coray
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News & Views |
Unwinding the mutational signatures of a DNA topoisomerase enzyme
Certain patterns of mutations occur frequently in cancer. The culprit behind one mutational signature is now shown to be a cellular enzyme with the mundane role of relieving stress in supercoiled DNA.
- Ammal Abbasi
- & Ludmil B. Alexandrov
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Article
| Open Access
Signatures of TOP1 transcription-associated mutagenesis in cancer and germline
Defective ribonucleotide excision repair causes ID4, an indel cancer signature characterized by deletions of 2–5 base pairs.
- Martin A. M. Reijns
- , David A. Parry
- & Andrew P. Jackson
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Article |
Brahma safeguards canalization of cardiac mesoderm differentiation
The BAF chromatin-remodelling complex ATPase gene Brm safeguards cell identity during directed cardiogenesis of mouse embryonic stem cells.
- Swetansu K. Hota
- , Kavitha S. Rao
- & Benoit G. Bruneau
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Article |
Ageing exacerbates ribosome pausing to disrupt cotranslational proteostasis
Ageing alters the kinetics of translation elongation in both Caenorhabditis elegans and Saccharomyces cerevisiae.
- Kevin C. Stein
- , Fabián Morales-Polanco
- & Judith Frydman
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World View |
Molecular biologists: let’s reconnect with nature
A New Year’s resolution for bench scientists is to step out of the lab to study how life really works.
- Edith Heard
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Article |
MicroRNA sequence codes for small extracellular vesicle release and cellular retention
MicroRNAs encode sorting sequences that determine whether they are secreted in exosomal vesicles to regulate gene expression in distant cells or retained in cells that produced them, with different sequences used by individual cell types.
- Ruben Garcia-Martin
- , Guoxiao Wang
- & C. Ronald Kahn
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Article
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Local and systemic responses to SARS-CoV-2 infection in children and adults
Mechanisms explaining the milder clinical syndrome that is observed in children with SARS-CoV-2 infection.
- Masahiro Yoshida
- , Kaylee B. Worlock
- & Kerstin B. Meyer
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Article
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Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer
PROTAC degrader–induced SWI/SNF inactivation abolishes DNA accessibility at enhancer elements of oncogenes and also tempers supra-physiologic expression of driver transcription factors, resulting in potent inhibition of tumour growth in mouse models.
- Lanbo Xiao
- , Abhijit Parolia
- & Arul M. Chinnaiyan
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Article |
Valine tRNA levels and availability regulate complex I assembly in leukaemia
Restriction of dietary valine reduces growth of T cell acute lymphoblastic leukaemia through altered valine tRNA biogenesis and reduced translation of mRNAs that encode subunits of mitochondrial complex I.
- Palaniraja Thandapani
- , Andreas Kloetgen
- & Iannis Aifantis
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Article
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HELQ is a dual-function DSB repair enzyme modulated by RPA and RAD51
HELQ is differentially regulated by RAD51, which stimulates helicase activity, and RPA, which inhibits helicase activity and stimulates annealing.
- Roopesh Anand
- , Erika Buechelmaier
- & Simon J. Boulton
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Correspondence |
Remembering a pioneer in biotechnology
- Tzvi Aviv
- , Frank Sicheri
- & Robert A. Weinberg
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Article |
Sex-specific chromatin remodelling safeguards transcription in germ cells
Following global DNA demethylation, mouse gonadal primordial germ cells undergo remodelling of repressive chromatin modifications, resulting in a sex-specific signature that is required to safeguard the transcriptional program.
- Tien-Chi Huang
- , Yi-Fang Wang
- & Petra Hajkova
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Article |
Non-genetic determinants of malignant clonal fitness at single-cell resolution
Non-genetic malignant clonal dominance is a cell-intrinsic and heritable property that underpins clonal output and response to therapy in cancer.
- Katie A. Fennell
- , Dane Vassiliadis
- & Mark A. Dawson
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Activation of homologous recombination in G1 preserves centromeric integrity
Centromeres are able to recruit the homologous recombination machinery during G1 via CENP-A and HJURP, thereby preserving centromeric integrity even in the absence of a sister chromatid.
- Duygu Yilmaz
- , Audrey Furst
- & Evi Soutoglou
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Accuracy mechanism of eukaryotic ribosome translocation
Structural analysis of the Saccharomyces cerevisiae 80S ribosome trapped in an intermediate translocation state shows stabilization of codon–anticodon interactions by eukaryote-specific elements of the 80S ribosome, eEF2 and tRNA and demonstrates a major role for eEF2 in maintaining the directionality of translocation.
- Muminjon Djumagulov
- , Natalia Demeshkina
- & Gulnara Yusupova
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Article |
De novo protein design by deep network hallucination
The trRosetta neural network was used to iteratively optimise model proteins from random 100-amino-acid sequences, resulting in ‘hallucinated’ proteins, which when expressed in bacteria closely resembled the model structures.
- Ivan Anishchenko
- , Samuel J. Pellock
- & David Baker
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Aldehyde-driven transcriptional stress triggers an anorexic DNA damage response
Endogenous formaldehyde accumulation reveals Cockayne syndrome in mice and stimulates production of the anorexiogenic peptide GDF15 in proximal tubule cells.
- Lee Mulderrig
- , Juan I. Garaycoechea
- & Ketan J. Patel
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FAM72A antagonizes UNG2 to promote mutagenic repair during antibody maturation
FAM72A differentially controls mutation rates by regulating uracil processing at different stages of the cell cycle, thereby regulating somatic hypermutation and class-switch recombination in B cells.
- Yuqing Feng
- , Conglei Li
- & Alberto Martin
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News |
COVID’s career impact and embryo secrets — the week in infographics
Nature highlights three key infographics from the week in science and research.
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Article
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Genome surveillance by HUSH-mediated silencing of intronless mobile elements
The human silencing hub (HUSH) complex uses introns to distinguish intronless foreign DNA from intron-containing host DNA and modifies chromatin to silence transcription of retrotransposons and retroviruses.
- Marta Seczynska
- , Stuart Bloor
- & Paul J. Lehner
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Nature Index |
Canada’s scientists are elucidating the dark metabolome
Teams studying the human body at the molecular level are grappling with matter that defies identification.
- James Mitchell Crow
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News & Views |
A peek into the black box of human embryology
The molecular mechanisms involved in human gastrulation, a crucial stage in early embryonic development, have been largely elusive. Gene-expression data from a gastrulating human embryo shed light on this process.
- Alexander Goedel
- & Fredrik Lanner
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Article
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Cell-type specialization is encoded by specific chromatin topologies
A new technique called immunoGAM, which combines genome architecture mapping (GAM) with immunoselection, enabled the discovery of specialized chromatin conformations linked to gene expression in specific cell populations from mouse brain tissues.
- Warren Winick-Ng
- , Alexander Kukalev
- & Ana Pombo
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Article |
Structural insights into Ubr1-mediated N-degron polyubiquitination
Structures of Ubr1 in complex with Ubc2, ubiquitin and two N-degron peptides reveal a Ubc2-binding region and an acceptor ubiquitin-binding loop on Ubr1, providing mechanistic insights into the initiation and elongation steps of ubiquitination catalysed by Ubr1.
- Man Pan
- , Qingyun Zheng
- & Minglei Zhao
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Target site selection and remodelling by type V CRISPR-transposon systems
Structural studies on Scytonema hofmanni CRISPR-associated transposon protein complexes indicate a mechanism for RNA-guided DNA transposition involving Cas12k, TnsC and TnsB.
- Irma Querques
- , Michael Schmitz
- & Martin Jinek
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Article
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Cold-induced Arabidopsis FRIGIDA nuclear condensates for FLC repression
In Arabidopsis thaliana, downregulation of the floral repressor FLC in response to cold occurs through a mechanism in which the FLC activator FRIGIDA is sequestered into biomolecular condensates away from the FLC promoter.
- Pan Zhu
- , Clare Lister
- & Caroline Dean
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Technology Feature |
Refining the toolkit for sugar analysis
Antibodies and other reagents for glycans have lagged behind those for proteins and nucleic acids, but the field is catching up.
- Amber Dance
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Article
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A conserved mechanism for regulating replisome disassembly in eukaryotes
A conserved mechanism for the regulation of replisome disassembly in eukaryotes is shown using cryo-electron microscopy, revealing a role for DNA in the preservation of replisome integrity.
- Michael Jenkyn-Bedford
- , Morgan L. Jones
- & Tom D. Deegan
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Article |
eccDNAs are apoptotic products with high innate immunostimulatory activity
By developing a new eccDNA purification and profiling method, the study revealed close-to-random genomic origination, mechanism of biogenesis and function of eccDNAs.
- Yuangao Wang
- , Meng Wang
- & Yi Zhang
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Article
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Transposon-associated TnpB is a programmable RNA-guided DNA endonuclease
The RNA-directed nuclease TnpB from Deinococcus radiodurans can be reprogrammed to cleave DNA target sites in human cells.
- Tautvydas Karvelis
- , Gytis Druteika
- & Virginijus Siksnys
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Article
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DNA methylation atlas of the mouse brain at single-cell resolution
A comprehensive survey of the epigenome from 45 regions of the mouse cortex, hippocampus, striatum, pallidum and olfactory areas using single-nucleus DNA methylation sequencing enables identification of 161 cell clusters with distinct locations and projection targets and provides insights into the regulatory landscape underlying neuronal diversity and spatial regulation.
- Hanqing Liu
- , Jingtian Zhou
- & Joseph R. Ecker
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Article |
Mechanism for Cas4-assisted directional spacer acquisition in CRISPR–Cas
Structures of the Cas4–Cas1–Cas2 complex from Geobacter sulfurreducens show that a 3′-overhang in the protospacer adjacent motif is required for complex assembly and spacer insertion into the CRISPR array.
- Chunyi Hu
- , Cristóbal Almendros
- & Ailong Ke
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News & Views |
Protein condensates provide a platform for controlling chromatin
The protein UTX regulates the DNA–protein complex chromatin to suppress tumour growth. Data suggest that the ability of UTX to condense into liquid-like droplets underlies its chromatin-regulating ability.
- David Lara-Astiaso
- & Brian J. P. Huntly
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Article
| Open Access
Structural basis of human transcription–DNA repair coupling
The authors resolve the structure of five complexes containing RNA polymerase II and the CSA and CSB proteins, offering insight into how the repair of DNA lesions is coupled to transcription.
- Goran Kokic
- , Felix R. Wagner
- & Patrick Cramer
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Article |
UTX condensation underlies its tumour-suppressive activity
Phase separation properties are a major determinant of UTX activity in chromatin regulation in tumour suppression, and are dependent on a core intrinsically disordered region of the protein.
- Bi Shi
- , Wei Li
- & Hao Jiang
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Article |
Single-cell Ribo-seq reveals cell cycle-dependent translational pausing
Highly sensitive ribosome profiling of single cells at single-codon resolution enables identification of distinct cell cycle-dependent translational dynamic states in individual cells.
- Michael VanInsberghe
- , Jeroen van den Berg
- & Alexander van Oudenaarden
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Article |
Programmable RNA targeting with the single-protein CRISPR effector Cas7-11
Cas7-11—the fusion of a putative Cas11 domain and four Cas7 subunits—cleaves RNA without detectable non-specific activity and, when optimized for RNA knockdown and editing in mammalian cells, has no effects on cell viability.
- Ahsen Özcan
- , Rohan Krajeski
- & Jonathan S. Gootenberg
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Article
| Open Access
RecA finds homologous DNA by reduced dimensionality search
Observations of rapid repair of double-stranded DNA breaks in sister choromosomes in Escherichia coli are consistent with a reduced-dimensionality-search model of RecA-mediated repair.
- Jakub Wiktor
- , Arvid H. Gynnå
- & Johan Elf
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Article |
Structural basis for piRNA targeting
Cryo-electron microscopy structures of a PIWI–piRNA complex provide insight into how piRNAs recognise target RNAs and reveal differences from the target mechanisms of microRNAs.
- Todd A. Anzelon
- , Saikat Chowdhury
- & Ian J. MacRae
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Article |
DAXX represents a new type of protein-folding enabler
A protein chaperone system is identified that consists of proteins with poly-Asp/Glu sequence, and may have an important role in diseases characterized by protein aggregation.
- Liangqian Huang
- , Trisha Agrawal
- & Xiaolu Yang
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Article |
Molecular basis for DarT ADP-ribosylation of a DNA base
Structural and mechanistic data of the ADP-ribosyltransferase DarT demonstrate the role of ADP-ribosylation of DNA by this enzyme in generating toxicity and regulating cellular signalling processes in bacteria.
- Marion Schuller
- , Rachel E. Butler
- & Ivan Ahel
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Article |
Cotranslational prolyl hydroxylation is essential for flavivirus biogenesis
A proteomics-based strategy is used to examine how three different RNA viruses (polio, Zika and dengue) remodel translation in the host to recruit host machineries necessary for the production of viral proteins.
- Ranen Aviner
- , Kathy H. Li
- & Raul Andino
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News & Views |
Ubiquitin protein helps cells to recover from stress
In stressed cells, proteins and RNA molecules cluster together to form stress granules. It emerges that the small protein modifier ubiquitin is needed to disassemble stress granules in recovering cells.
- Titus Franzmann
- & Simon Alberti
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Review Article |
Exploring tissue architecture using spatial transcriptomics
This review describes the state of spatial transcriptomics technologies and analysis tools that are being used to generate biological insights in diverse areas of biology.
- Anjali Rao
- , Dalia Barkley
- & Itai Yanai
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Article |
Cryo-EM structures of full-length Tetrahymena ribozyme at 3.1 Å resolution
Cryo-electron microscopy has been used to determine the structure of the Tetrahymena ribozyme (a catalytic RNA) at sufficiently high resolution to model side chains and metal ions.
- Zhaoming Su
- , Kaiming Zhang
- & Wah Chiu
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Review Article |
The role of retrotransposable elements in ageing and age-associated diseases
This Review discusses how the activity of retrotransposons influences ageing and the role of these mobile genetic elements in age-related diseases and their treatment.
- Vera Gorbunova
- , Andrei Seluanov
- & John M. Sedivy
Structural basis for mismatch surveillance by CRISPR–Cas9Browse broader subjects
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- Cell division
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- CRISPR-Cas systems
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- DNA metabolism
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- DNA replication
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- Non-coding RNAs
- Nuclear organization
- Post-translational modifications
- Protein folding
- Proteolysis
- Proteomics
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- Ribozymes
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- Single-molecule biophysics
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