News & Views |
Featured
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Article |
Structural basis for outer membrane lipopolysaccharide insertion
Lipopolysaccharide, an essential component of the outer membranes of Gram-negative bacteria, is inserted by LptD–LptE, a protein complex with a unique ‘barrel and plug’ architecture; the structure, molecular dynamics simulations and functional assays of the LptD–LptE complex of Salmonella typhimurium suggest that lipopolysaccharide may pass through the barrel and is then inserted into the outer leaflet of the outer membrane through a lateral opening between two β-strands of LptD.
- Haohao Dong
- , Quanju Xiang
- & Changjiang Dong
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News & Views |
Wobble puts RNA on target
Enzymes that attach amino acids to transfer RNAs during protein synthesis must recognize both substrates specifically. Crystal structures reveal a mechanism that explains the RNA specificity for one such system. See Article p.507
- Oscar Vargas-Rodriguez
- & Karin Musier-Forsyth
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Letter |
Dynamic pathways of −1 translational frameshifting
To investigate the mechanism of frameshifting during messenger RNA translation, a technique was developed to monitor translation of single molecules in real time using Förster resonance energy transfer (FRET); ribosomes were revealed to pause tenfold longer than usual during elongation at the frameshifting sites.
- Jin Chen
- , Alexey Petrov
- & Joseph D. Puglisi
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Article |
The selective tRNA aminoacylation mechanism based on a single G•U pair
X-ray crystal structures of a tRNA synthetase bound to wild-type and mutant alanine tRNAs reveal the structural basis for selectivity.
- Masahiro Naganuma
- , Shun-ichi Sekine
- & Shigeyuki Yokoyama
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News & Views |
Short RNAs and shortness of breath
The simultaneous deletion of six RNA molecules in mice has been found to cause respiratory and fertility defects, owing to improper assembly of structures called cilia on the cell surface. See Article p.115
- Irma Sánchez
- & Brian D. Dynlacht
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Books & Arts |
Molecular biology: Of DNA and broken dreams
Georgina Ferry weighs up a life of William Astbury, who had a forgotten role in pinning down the double helix.
- Georgina Ferry
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Article |
miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110
Loss-of-function studies of the miR-34/449 microRNA family in mouse and Xenopus reveal their evolutionarily conserved role in ciliogenesis by repressing expression of the centriolar protein Cp110.
- Rui Song
- , Peter Walentek
- & Lin He
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News |
Flashes of light show how memories are made
Researchers confirm cellular basis for memory by implanting and erasing fear into the brains of rats using fibre optics.
- Ewen Callaway
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News |
Computer model predicts academic success
Algorithm based on publications finds that first-author articles in leading journals matter most.
- Richard Van Noorden
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Letter |
Avoidance of ribonucleotide-induced mutations by RNase H2 and Srs2-Exo1 mechanisms
Srs2 helicase facilitates the removal of ribonucleoside monophosphates that are incorrectly incorporated into DNA during replication.
- Catherine J. Potenski
- , Hengyao Niu
- & Hannah L. Klein
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Letter |
BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor PCID2
BRCA2, the breast cancer susceptibility gene factor, interacts with TREX-2, a protein complex involved in the biogenesis and export of messenger ribonucleoprotein, to process DNA–RNA hybrid structures called R-loops that can trigger genome instability; these may be a central cause of the stress occurring in early cancer cells that drives oncogenesis.
- Vaibhav Bhatia
- , Sonia I. Barroso
- & Andrés Aguilera
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Letter |
Analysis of orthologous groups reveals archease and DDX1 as tRNA splicing factors
Using a phylogenetic approach, the protein archease is identified as being a subunit of the human transfer RNA splicing ligase, and found to be necessary for full ligase activity, in cooperation with DDX1.
- Johannes Popow
- , Jennifer Jurkin
- & Javier Martinez
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News & Views |
Enzyme meets a surprise target
An enzyme previously implicated in gene regulation has now been found to have a role in cancer progression, potentiating an intracellular signalling pathway that is driven by a mutated K-Ras protein. See Letter p.283
- Marian M. Deuker
- & Martin McMahon
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Letter |
SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer
SMYD3 is a methyltransferase overexpressed in several human tumours; here methylation of the MAP3K2 kinase by SMYD3 is shown to be critical for Ras-induced tumour development in mouse models and human tumour cells, showing an unexpected role for methylation in a kinase signalling pathway and revealing a candidate therapeutic target.
- Pawel K. Mazur
- , Nicolas Reynoird
- & Or Gozani
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News |
Video reveals entire organism's neurons at work
Researchers image complete nervous system in real time.
- Sara Reardon
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News & Views |
Female silkworms have the sex factor
Sex determination in the silkworm Bombyx mori has been found to depend on the presence or absence of a small RNA. This is thought to be the first example of a molecule other than a protein mediating this process. See Letter p.633
- František Marec
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Article |
Structural basis of the non-coding RNA RsmZ acting as a protein sponge
A novel combined NMR and EPR spectroscopy approach reveals the structure and assembly mechanism of a 70-kDa bacterial ribonucleoprotein complex acting as a protein sponge in translational regulation.
- Olivier Duss
- , Erich Michel
- & Frédéric H.-T. Allain
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Letter |
CFIm25 links alternative polyadenylation to glioblastoma tumour suppression
CFIm25 is identified as a factor that prevents messenger RNAs being shortened due to altered 3′ polyadenylation, which typically occurs when cells undergo high proliferation and correlates with increased tumorigenic activity in glioblastoma tumours.
- Chioniso P. Masamha
- , Zheng Xia
- & Eric J. Wagner
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News & Views |
Construction of a yeast chromosome
One aim of synthetic biology is to generate complex synthetic organisms. Now, a stage in this process has been achieved in yeast cells — an entire yeast chromosome has been converted to a synthetic sequence in a stepwise manner.
- Daniel G. Gibson
- & J. Craig Venter
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News & Views |
New letters for life's alphabet
The five bases found in nucleic acids define the 'alphabet' used to encode life on Earth. The construction of an organism that stably propagates an unnatural DNA base pair redefines this fundamental feature of life. See Letter p.385
- Ross Thyer
- & Jared Ellefson
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Letter |
A semi-synthetic organism with an expanded genetic alphabet
Triphosphates of hydrophobic nucleotides d5SICS and dNaM are imported into Escherichia coli by an exogenous algal nucleotide triphosphate transporter and then used by an endogenous polymerase to replicate, and faithfully maintain over many generations of growth, a plasmid containing the d5SICS–dNaM unnatural base pair.
- Denis A. Malyshev
- , Kirandeep Dhami
- & Floyd E. Romesberg
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Letter |
BRCA1 controls homologous recombination at Tus/Ter-stalled mammalian replication forks
Direct evidence for the role of BRCA1 in controlling homologous recombination at stalled replication forks has been obtained in mammalian cells using the bacterial Tus/Ter system.
- Nicholas A. Willis
- , Gurushankar Chandramouly
- & Ralph Scully
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News & Views |
Sperm protein finds its mate
Knowledge of the sperm-specific protein that is required for the attachment of sperm to eggs during fertilization in mammals has led to the identification of the protein's receptor on the egg's plasma membrane. See Article p.483
- Paul M. Wassarman
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News & Views |
Up and down in Down's syndrome
A comparison of identical human twins, only one of whom has Down's syndrome, reveals a genome-wide flattening of gene-expression levels in the affected individual. See Article p.345
- Benjamin D. Pope
- & David M. Gilbert
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News |
Sperm RNA carries marks of trauma
Stress alters the expression of small RNAs in male mice and leads to depressive behaviours in later generations.
- Virginia Hughes
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Research Highlights |
DNA regulator acts on RNA too
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Article |
Homologue engagement controls meiotic DNA break number and distribution
DNA double-stranded breaks (DSBs) are shown to form in greater numbers in yeast cells lacking ZMM proteins, which are traditionally regarded as acting strictly downstream of DSB formation; these findings shed light on how cells balance the beneficial and deleterious outcomes of DSB formation.
- Drew Thacker
- , Neeman Mohibullah
- & Scott Keeney
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News & Views |
Damage prevention targeted
The MTH1 protein prevents oxidized nucleotides from being misincorporated into DNA. Two studies find that selective inhibition of MTH1 by small molecules suppresses tumour growth. See Articles p.215 & p.222
- Dan Dominissini
- & Chuan He
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Article |
MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
In order to find a general treatment for cancer, this study found that MTH1 activity is essential for the survival of transformed cells, and isolated two small-molecule inhibitors of MTH1, TH287 and TH588 — in the presence of these inhibitors, damaged nucleotides are incorporated into DNA only in cancer cells, causing cytotoxicity and eliciting a beneficial response in patient-derived mouse xenograft models.
- Helge Gad
- , Tobias Koolmeister
- & Thomas Helleday
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Article |
An atlas of active enhancers across human cell types and tissues
Using the FANTOM5 CAGE expression atlas, the authors show that bidirectional capped RNAs are a signature feature of active enhancers and identify over 40,000 enhancer candidates from over 800 human cell and tissue samples across the whole human body.
- Robin Andersson
- , Claudia Gebhard
- & Albin Sandelin
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Article |
A promoter-level mammalian expression atlas
A study from the FANTOM consortium using single-molecule cDNA sequencing of transcription start sites and their usage in human and mouse primary cells, cell lines and tissues reveals insights into the specificity and diversity of transcription patterns across different mammalian cell types.
- Alistair R. R. Forrest
- , Hideya Kawaji
- & Yoshihide Hayashizaki
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News |
Human nose can detect 1 trillion odours
What the the nose knows might as well be limitless, researchers suggest.
- Jessica Morrison
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Research Highlights |
How proteins find their DNA target
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Letter |
Structural basis for translocation by AddAB helicase–nuclease and its arrest at χ sites
A dual-function helicase–nuclease, typified by RecBCD in Escherichia coli, acts on free DNA ends during bacterial double-stranded break repair until it reaches a χ sequence at which it pauses before continuing with modified enzymatic properties; here several crystal structures of the related AddAB enzyme from Bacillus subtilis bound to χ-containing DNA are presented, offering insight into χ recognition and its effect on DNA translocation.
- Wojciech W. Krajewski
- , Xin Fu
- & Dale B. Wigley
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Letter |
miRNAs trigger widespread epigenetically activated siRNAs from transposons in Arabidopsis
The generation of widespread epigenetically activated short interfering RNAs by the targeting of microRNAs to transposon transcripts in Arabidopsis thaliana is shown to be a latent mechanism that only becomes active when the transcripts are epigenetically reactivated, for example, during reprogramming of the germ line.
- Kate M. Creasey
- , Jixian Zhai
- & Robert A. Martienssen
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News |
New contender for 'fat gene' found
Researchers may have been focusing on the wrong gene.
- Brian Owens
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Letter |
Obesity-associated variants within FTO form long-range functional connections with IRX3
Obesity-associated noncoding sequences within FTO are functionally connected with IRX3, and long-range enhancers in this region recapitulate aspects of IRX3 expression, suggesting that the obesity-associated interval is part of IRX3 regulation; Irx3-deficient mice have lower body weight and are resistant to diet-induced obesity, suggesting IRX3 as a novel determinant of body mass and composition.
- Scott Smemo
- , Juan J. Tena
- & Marcelo A. Nóbrega
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News & Views |
G-quadruplex poses quadruple threat
Multiplication of repetitive DNA sequences is often the cause of neurodegenerative diseases. A four-stranded structure has been found to form in one such expansion in the gene C9orf72, altering gene function in four ways. See Article p.195
- J. Paul Taylor
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News Feature |
Epigenetics: The sins of the father
The roots of inheritance may extend beyond the genome, but the mechanisms remain a puzzle.
- Virginia Hughes
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Article |
C9orf72 nucleotide repeat structures initiate molecular cascades of disease
Structurally polymorphic C9orf72 hexanucleotide repeats cause an impairment in transcriptional processivity and lead to accumulation of truncated repeat-containing transcripts that bind to specific ribonucleoproteins, such as nucleolin, in a conformation-dependent manner resulting in nucleolar stress and C9orf72-linked pathology in amyotrophic lateral sclerosis and frontotemporal dementia.
- Aaron R. Haeusler
- , Christopher J. Donnelly
- & Jiou Wang
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Letter |
ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression
Candidate tumour suppressor ZMYND11 specifically recognizes histone K36 trimethylation on the histone variant H3.3 and helps regulate transcription elongation.
- Hong Wen
- , Yuanyuan Li
- & Xiaobing Shi
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Research Highlights |
Antifreeze protein has a heart of ice
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News & Views |
Tumours outside the mutation box
Analyses of ependymoma brain tumours reveal a gene rearrangement in one subtype, but no DNA mutations in two others, suggesting that mechanisms for cancer initiation are broader than is typically thought. See Articles p.445 & p.451
- Rogier Versteeg
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Letter |
Two independent transcription initiation codes overlap on vertebrate core promoters
The transcription start sites used during the maternal to zygotic transition in zebrafish are mapped, revealing that the transition is characterized by a switch between two different sequence signs to guide transcription initiation, which often co-exist in core promoters.
- Vanja Haberle
- , Nan Li
- & Boris Lenhard
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Letter |
DNA-guided DNA interference by a prokaryotic Argonaute
Here, Argonaute from the prokaryote Thermus thermophilus is shown to use small DNA guides to interfere directly with invading foreign DNA, rather than being involved in RNA-guided RNA interference, as observed in eukaryotes.
- Daan C. Swarts
- , Matthijs M. Jore
- & John van der Oost
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News & Views |
Protein binding cannot subdue a lively RNA
Ribosomes, the cell's protein-synthesis machines, are assembled from their components in a defined order. It emerges that the first assembly step must overcome dynamic structural rearrangements. See Article p.334
- Kathleen B. Hall
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Article |
Protein-guided RNA dynamics during early ribosome assembly
Three-colour fluorescence resonance energy transfer and molecular dynamics simulations are used to study the events occurring early in assembly of the 30S ribosome; within a non-native intermediate S4 ribosomal protein–16S RNA structure, S4 is capable of altering the RNA helix dynamics to facilitate conformation changes that enable subsequent protein binding.
- Hajin Kim
- , Sanjaya C. Abeysirigunawarden
- & Sarah A. Woodson
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Research Highlights |
CRISPR makes modified monkeys
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