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Article |
Basis of narrow-spectrum activity of fidaxomicin on Clostridioides difficile
Structural analysis of Clostridioides difficile RNA polymerase in complex with fidaxomicin combined with biochemical, genetic and bioinformatic analyses identifies a key residue that determines fidaxomicin sensitivity.
- Xinyun Cao
- , Hande Boyaci
- & Elizabeth A. Campbell
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News & Views |
An added layer of repression for human genes
A protein complex called the rixosome helps to degrade RNA transcripts that linger after gene expression ceases. This discovery points to distinct roles for the rixosome in regulating chromatin in different species.
- Michael Uckelmann
- & Chen Davidovich
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Article
| Open Access
Rixosomal RNA degradation contributes to silencing of Polycomb target genes
The rixosome associates with Polycomb repressive complexes and chromatin and has a role in silencing of Polycomb target gene expression in human cells via degradation of nascent RNA transcripts.
- Haining Zhou
- , Chad B. Stein
- & Danesh Moazed
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Article |
Targeting Xist with compounds that disrupt RNA structure and X inactivation
A molecule identified in a screen for compounds that bind the non-coding mouse RNA Xist blocks Xist-dependent X-chromosome inactivation, demonstrating the utility of this approach for identifying drugs that target RNA.
- Rodrigo Aguilar
- , Kerrie B. Spencer
- & Jeannie T. Lee
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Article |
Crucial role and mechanism of transcription-coupled DNA repair in bacteria
Integrated structure–function studies show that transcription-coupled DNA repair (TCR)—rather than global genomic repair—is responsible for most chromosomal repair events in bacteria, and that TCR mainly occurs independently of the Mfd translocase.
- Binod K. Bharati
- , Manjunath Gowder
- & Evgeny Nudler
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Article |
N6-methyladenosine in poly(A) tails stabilize VSG transcripts
N6-methyladenosine is enriched in poly(A) tails of VSG transcripts in Trypanosoma brucei, and when lacking result in mRNA degradation.
- Idálio J. Viegas
- , Juan Pereira de Macedo
- & Luisa M. Figueiredo
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Article
| Open Access
A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic
A small-molecule inhibitor of TMPRSS2 is effective against SARS-CoV-2 variants of concern in human lung cells and in donor-derived colonoids, and also shows prophylactic and therapeutic benefits in a mouse model of COVID-19.
- Tirosh Shapira
- , I. Abrrey Monreal
- & François Jean
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Technology Feature |
Molecular barcodes reveal tumour lineages
Researchers are blending tools from developmental biology with technologies such as cell sorting and CRISPR to gain fresh insight into cancer.
- Jyoti Madhusoodanan
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Obituary |
François Gros (1925–2022)
Co-discoverer of messenger RNA who advanced French life sciences.
- Georgina Ferry
-
News & Views |
AI predicts the effectiveness and evolution of gene promoter sequences
A long-standing goal of biology is the ability to predict gene expression from DNA sequence. A type of artificial intelligence known as a neural network, combined with high-throughput experiments, now brings this goal a step closer.
- Andreas Wagner
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Article |
Bacterial ribosome collision sensing by a MutS DNA repair ATPase paralogue
Bacterial MutS2, a paralogue of the DNA mismatch-repair protein MutS, is found to bind collided ribosomes and function in translational quality control.
- Federico Cerullo
- , Sebastian Filbeck
- & Claudio A. P. Joazeiro
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Article
| Open Access
Tryptophan depletion results in tryptophan-to-phenylalanine substitutants
Tryptophan depletion, which occurs in tumours, results in in-frame translation across tryptophan-encoding codons by phenylalanine substitution.
- Abhijeet Pataskar
- , Julien Champagne
- & Reuven Agami
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Article |
Ribosome collisions induce mRNA cleavage and ribosome rescue in bacteria
In bacteria, a newly identified endonuclease activated by ribosome collisions truncates mRNA to trigger rescue of stalled ribosomes.
- Kazuki Saito
- , Hanna Kratzat
- & Allen R. Buskirk
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Outline |
Video: Guardian of the genome
The tumour-suppressing protein p53 protects our cells from damage, and its malfunction is associated with a vast array of cancers. There are no drugs to restore p53 function in tumours yet, but several therapies are under development.
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Outline |
p53: an anticancer protein’s chequered past and promising future
After a mixed-up start, it is now understood that most tumours exhibit dysfunction of the protein p53. Restoring its tumour-suppressing properties is no easy task.
- Michael Eisenstein
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Outline |
A visual guide to restoring the guardian of the genome
Many tumours exhibit dysfunction of the p53 protein, a crucial suppressor of cancer. But, because the cause of this dysfunction varies, so, too, must potential treatments.
- Michael Eisenstein
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Research Briefing |
Determining the structure of fleeting protein states
Proteins adopt unstable, high-energy states that exist for fractions of a second but can have key biological roles. A new method of determining high-resolution structures of such states using a form of nuclear magnetic resonance reveals how small changes in protein shape are essential to their function.
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Article
| Open Access
Structural basis for mismatch surveillance by CRISPR–Cas9
Cryo-electron microscopy structures of Cas9 during mismatch cleavage provide insight into the mechanisms that control off-target effects of Cas9, which will aid in the future design of high-fidelity Cas9 variants with reduced off-target cleavage.
- Jack P. K. Bravo
- , Mu-Sen Liu
- & David W. Taylor
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Article |
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
| Open Access
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
| Open Access
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
| Open Access
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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Article |
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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Article
| Open Access
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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Article |
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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Article |
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
| Open Access
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
| Open Access
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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Article |
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
| Open Access
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
-
Article
| Open Access
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
Democratizing the mapping of gene mutations to protein biophysics
Basis of narrow-spectrum activity of fidaxomicin on Clostridioides difficile
An added layer of repression for human genes
Rixosomal RNA degradation contributes to silencing of Polycomb target genes
Targeting Xist with compounds that disrupt RNA structure and X inactivation
Crucial role and mechanism of transcription-coupled DNA repair in bacteria
N6-methyladenosine in poly(A) tails stabilize VSG transcripts
A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic
Molecular barcodes reveal tumour lineages
François Gros (1925–2022)
AI predicts the effectiveness and evolution of gene promoter sequences
Bacterial ribosome collision sensing by a MutS DNA repair ATPase paralogue
Tryptophan depletion results in tryptophan-to-phenylalanine substitutants
Ribosome collisions induce mRNA cleavage and ribosome rescue in bacteria
Video: Guardian of the genome
p53: an anticancer protein’s chequered past and promising future
A visual guide to restoring the guardian of the genome
Determining the structure of fleeting protein states
Structural basis for mismatch surveillance by CRISPR–Cas9
Molecular hallmarks of heterochronic parabiosis at single-cell resolution
A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk
Unwinding the mutational signatures of a DNA topoisomerase enzyme
Signatures of TOP1 transcription-associated mutagenesis in cancer and germline
Brahma safeguards canalization of cardiac mesoderm differentiation
Ageing exacerbates ribosome pausing to disrupt cotranslational proteostasis
Molecular biologists: let’s reconnect with nature
MicroRNA sequence codes for small extracellular vesicle release and cellular retention
Local and systemic responses to SARS-CoV-2 infection in children and adults
Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer
Valine tRNA levels and availability regulate complex I assembly in leukaemia
HELQ is a dual-function DSB repair enzyme modulated by RPA and RAD51
Sex-specific chromatin remodelling safeguards transcription in germ cells
Non-genetic determinants of malignant clonal fitness at single-cell resolution
Activation of homologous recombination in G1 preserves centromeric integrity
Accuracy mechanism of eukaryotic ribosome translocation
De novo protein design by deep network hallucination
Aldehyde-driven transcriptional stress triggers an anorexic DNA damage response
FAM72A antagonizes UNG2 to promote mutagenic repair during antibody maturation
COVID’s career impact and embryo secrets — the week in infographics
Genome surveillance by HUSH-mediated silencing of intronless mobile elements
Canada’s scientists are elucidating the dark metabolome
A peek into the black box of human embryology
Cell-type specialization is encoded by specific chromatin topologies
Structural insights into Ubr1-mediated N-degron polyubiquitination
Target site selection and remodelling by type V CRISPR-transposon systems
Cold-induced Arabidopsis FRIGIDA nuclear condensates for FLC repression
Refining the toolkit for sugar analysis
A conserved mechanism for regulating replisome disassembly in eukaryotesBrowse broader subjects
Browse narrower subjects
- Cell division
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- DNA damage and repair
- DNA metabolism
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- DNA replication
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- Post-translational modifications
- Protein folding
- Proteolysis
- Proteomics
- Riboswitches
- Ribozymes
- RNA metabolism
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