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Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more, covering all



 



Trump faces backlash on health-agency cuts

2017-03-17

Crippling the US National Institutes of Health might increase resistance to other attacks on science.



The FDA chief must not be a proxy for industry

2017-03-17

Trump’s pick for the US regulatory agency will bring experience and a clear vision — as well as ties to industry.



Birds of play demonstrate the infectious power of emotion

2017-03-22

New Zealand parrots provide the latest support for a popular theory of crowd behaviour.



Europe can build on scientific intuition

2017-03-21

Carlos Moedas sees a bold future for the European Research Council and more projects that copy its approach.



Materials: Graphene layers give colourful warning

2017-03-22

A material made of overlapping layers of graphene (atom-thick sheets of carbon) changes colour according to the level of stress applied. This could be used in structures to provide early warning of damage.A team led by Shanglin Gao of the Leibniz Institute of Polymer



Virology: Viruses switch hosts to evolve

2017-03-22

Viruses more often evolve by jumping from one host species to another than by remaining within a particular species.Edward Holmes and his colleagues at the University of Sydney in Australia compared the evolutionary histories of 19 virus families with those of their animal or



Developmental biology: Fatty bones weaken with age

2017-03-22

The build-up of fat cells in the bone marrow could explain why bones grow weaker and heal more slowly with age.Tim Schulz at the German Institute of Human Nutrition in Potsdam-Rehbrücke and his colleagues identified a population of stem-cell-like cells in the bones of



Astronomy: Star orbits close to black hole

2017-03-22

A white dwarf star that circles a black hole every 28 minutes may have the closest orbit of its kind ever seen in our Galaxy.The system, called 47 Tuc X9, is some 4.5 kiloparsecs away. It was already thought to contain two objects orbiting



Energy: Sodium battery packs a punch

2017-03-22

A cheap, rechargeable sodium-based battery could one day deliver high power at room temperature thanks to its hybrid solid electrolyte.Electrolytes allow electrical charge to flow between a battery's electrodes. Liquid electrolytes can leak and tend to react with sodium metal, an abundant, low-cost material



Climate-change biology: Heat could lead to tiny mammals

2017-03-22

Mammals might respond to global warming by shrinking in size.During a large warming event called the Palaeocene–Eocene Thermal Maximum (PETM), some 56 million years ago, mammals became smaller. To see how common this climate-driven dwarfing might have been, Abigail D'Ambrosia of the University of



Animal behaviour: Kingsnakes go for the big squeeze

2017-03-22

Kingsnakes have superior crushing power, allowing them to squeeze bigger snakes to death, even when these snakes are also constrictors.David Penning at Missouri Southern State University in Joplin and Brad Moon at the University of Louisiana at Lafayette studied 182 snakes from six species,



Evolution: Oldest algal fossils found

2017-03-22

Fossils of organisms resembling red algae suggest that multicellular life may have emerged on Earth some 400 million years earlier than previously thought.Fossils of the earliest algae — which are closely related to the ancestors of modern plants — are rare and, until now,



Drug discovery: CRISPR finds drug synergy

2017-03-22

Certain combinations of drugs might kill drug-resistant tumours, and a method based on the CRISPR–Cas9 gene-editing system offers a way to find them.Tumours often become resistant to individual drugs, leading clinicians to use combinations of medicines in the hope of thwarting resistance. Michael Bassik



Nuclear-test films, smoking declines and five new particles

2017-03-22

The week in science: 17–23 March 2017.



US science agencies face deep cuts in Trump budget

2017-03-16

The Environmental Protection Agency and the National Institutes of Health are big losers — but planetary science at NASA stands to gain.



Mathematicians create warped worlds in virtual reality

2017-03-21

Immersive experience set to become accessible to all.



South Korea’s scientists seek change amid political chaos

2017-03-22

President’s impeachment creates opportunity to shift how nation supports basic research.



South Africa’s San people issue ethics code to scientists

2017-03-20

The indigenous people — known for their click languages — are the first in Africa to draft guidelines for researchers.



‘Wavelet revolution’ pioneer scoops top maths award

2017-03-21

Yves Meyer wins the Abel Prize for role in theory with data applications from digital cinema to pinpointing gravitational waves.



How to hunt for a black hole with a telescope the size of Earth

2017-03-22

Astronomers hope to grab the first images of an event horizon — the point of no return.



Predatory journals recruit fake editor

2017-03-22

An investigation finds that dozens of academic titles offered 'Dr Fraud' — a sham, unqualified scientist — a place on their editorial board. Katarzyna Pisanski and colleagues report.



Don't link carbon markets

2017-03-21

A global network of cap-and-trade systems would deliver greater complexity and fewer emissions cuts, warns Jessica F. Green.



Environmental sciences: Troubled waters on the Great Lakes

2017-03-22

Anna M. Michalak on the taming and invasion of Earth's largest fresh-water system.



Books in brief

2017-03-22

Barbara Kiser reviews five of the week's best science picks.



Evolution: Four takes on the evolution of art

2017-03-22

Nurin Veis tours a show on theories of creativity, curated by a quartet of scientists.



Corporate culture: protect idea factories

2017-03-22

It is unsurprising that universities have adopted corporate culture (Nature540, 315;10.1038/540315a2016), but surprising that they select such archaic models.Universities corporatize because they must raise funds through teaching, research and commercialization. They need to publish research results openly,



Renewable energy: Commercial hurdles to wave power

2017-03-22

The variable nature of wave power is the main reason why it is expensive and difficult to collect (see Z. L.WangNature542, 159–160;10.1038/542159a2017). Wave-power devices have much more demanding structural requirements than do offshore wind farms,



Politics: Listen to accused Turkish scientists

2017-03-22

In my view, you misrepresent aspects of the problems confronting scientists in Turkey (Nature542, 286–288;10.1038/542286a2017). As a Turkish scientist working abroad, I contend that Turkey's government is using its former political ally, the Gülen movement, as



Environment: China's decadal pollution census

2017-03-22

China will conduct its second decadal pollution census in December 2017. This will provide a baseline for measuring the impact of environmental taxes that come into force next year, and for assessing discharge permits that will be issued for all pollution sources by 2020. The



Chromatography: Shirts off to boost separation methods

2017-03-22

Shirts were a source of inspiration for starch-gel electrophoresis (E.AltschulerNature543, 179;10.1038/543179e2017). They also figured in another pioneering separation technique — polyamide thin-layer chromatography.At the National Taiwan University in 1958, Kung-Tsung Wang and Yao-Tang Lin heard



Eugene Garfield (1925–2017)

2017-03-22

Inventor of the Science Citation Index.



Research management: A delicate balance

2017-03-22

Conflicts of interest can send a researcher's reputation crashing — but resolving them needn't be as burdensome as it seems.



Turning point: Whale watcher

2017-03-22

Saving pygmy blue whales in Sri Lanka's shipping lanes.



Mr Singularity

2017-03-22

“Forty-five minutes exactly, no more.”I'd been trying to gain access to a Mr Singularity ever since the original self-iterated Mr Singularity 2.0, to no avail. The artificial-intelligence cabal knew I would use it to prove that their goal of creating artificial consciousness was inherently



Corrections

2017-03-21

The graphic in the News story ‘China seeks cosmic-ray win’ (Nature 543, 300–301; 2017) erroneously gave the surface area of the surface-water Cherenkov detector as 80 m2. In fact, the area is 80,000 m2. The News story ‘Ancient volcanoes



Palaeontology: Dividing the dinosaurs

2017-03-22

The standard dinosaur evolutionary tree has two key branches: the 'bird-hipped' Ornithischia and the 'reptile-hipped' Saurischia. A revised tree challenges many ideas about the relationships between dinosaur groups. See Article p.501



Microbiology: Bacterial transmission tactics

2017-03-22

Genome sequencing of Mycobacterium abscessus strains that infect the lungs suggests a possible shift in the bacterium's mode of infection from environmental acquisition to human transmission. This finding has clinical implications.



Condensed-matter physics: Vibrations mapped by an electron beam

2017-03-22

The vibrational excitations of nanostructures have been mapped using state-of-the-art electron microscopy. The results improve our understanding of these excitations, which will aid the design of nanostructures. See Letter p.529



Ecology: A helping habitat for bumblebees

2017-03-15

A study showing the effects of land-use quality on the productivity of bumblebee colonies highlights the importance of resource availability across space and time in promoting survival over generations. See Letter p.547



HIV: Finding latent needles in a haystack

2017-03-15

Antiretroviral therapy can keep HIV at bay, but a few cells remain infected, so the disease cannot be cured. The discovery of a protein that marks out these infected cells will facilitate crucial studies of this latent viral reservoir. See Letter p.564



A new hypothesis of dinosaur relationships and early dinosaur evolution

2017-03-22

For 130 years, dinosaurs have been divided into two distinct clades—Ornithischia and Saurischia. Here we present a hypothesis for the phylogenetic relationships of the major dinosaurian groups that challenges the current consensus concerning early dinosaur evolution and highlights problematic aspects of current cladistic definitions. Our



Autism gene Ube3a and seizures impair sociability by repressing VTA Cbln1

2017-03-15

Maternally inherited 15q11-13 chromosomal triplications cause a frequent and highly penetrant type of autism linked to increased gene dosages of UBE3A, which encodes a ubiquitin ligase with transcriptional co-regulatory functions. Here, using in vivo mouse genetics, we show that increasing UBE3A in the



Root microbiota drive direct integration of phosphate stress and immunity

2017-03-15

Plants live in biogeochemically diverse soils with diverse microbiota. Plant organs associate intimately with a subset of these microbes, and the structure of the microbial community can be altered by soil nutrient content. Plant-associated microbes can compete with the plant and with each other for



Complex multi-enhancer contacts captured by genome architecture mapping

2017-03-08

The organization of the genome in the nucleus and the interactions of genes with their regulatory elements are key features of transcriptional control and their disruption can cause disease. Here we report a genome-wide method, genome architecture mapping (GAM), for measuring chromatin contacts and other



Simultaneous tracking of spin angle and amplitude beyond classical limits

2017-03-22

Measurement of spin precession is central to extreme sensing in physics, geophysics, chemistry, nanotechnology and neuroscience, and underlies magnetic resonance spectroscopy. Because there is no spin-angle operator, any measurement of spin precession is necessarily indirect, for example, it may be inferred from spin projectors at different times. Such projectors do not commute, and so quantum measurement back-action—the random change in a quantum state due to measurement—necessarily enters the spin measurement record, introducing errors and limiting sensitivity. Here we show that this disturbance in the spin projector can be reduced below N1/2—the classical limit for N spins—by directing the quantum measurement back-action almost entirely into an unmeasured spin component. This generates a planar squeezed state that, because spins obey non-Heisenberg uncertainty relations, enables simultaneous precise knowledge of spin angle and spin amplitude. We use high-dynamic-range optical quantum non-demolition measurements applied to a precessing magnetic spin ensemble to demonstrate spin tracking with steady-state angular sensitivity 2.9 decibels below the standard quantum limit, simultaneously with amplitude sensitivity 7.0 decibels below the Poissonian variance. The standard quantum limit and Poissonian variance indicate the best possible sensitivity with independent particles. Our method surpasses these limits in non-commuting observables, enabling orders-of-magnitude improvements in sensitivity for state-of-the-art sensing and spectroscopy.



Mapping vibrational surface and bulk modes in a single nanocube

2017-03-22

Imaging of vibrational excitations in and near nanostructures is essential for developing low-loss infrared nanophotonics, controlling heat transport in thermal nanodevices, inventing new thermoelectric materials and understanding nanoscale energy transport. Spatially resolved electron energy loss spectroscopy has previously been used to image plasmonic behaviour in nanostructures in an electron microscope, but hitherto it has not been possible to map vibrational modes directly in a single nanostructure, limiting our understanding of phonon coupling with photons and plasmons. Here we present spatial mapping of optical and acoustic, bulk and surface vibrational modes in magnesium oxide nanocubes using an atom-wide electron beam. We find that the energy and the symmetry of the surface polariton phonon modes depend on the size of the nanocubes, and that they are localized to the surfaces of the nanocube. We also observe a limiting of bulk phonon scattering in the presence of surface phonon modes. Most phonon spectroscopies are selectively sensitive to either surface or bulk excitations; therefore, by demonstrating the excitation of both bulk and surface vibrational modes using a single probe, our work represents advances in the detection and visualization of spatially confined surface and bulk phonons in nanostructures.



Mechanical metamaterials at the theoretical limit of isotropic elastic stiffness

2017-02-20

A wide variety of high-performance applications require materials for which shape control is maintained under substantial stress, and that have minimal density. Bio-inspired hexagonal and square honeycomb structures and lattice materials based on repeating unit cells composed of webs or trusses, when made from materials of high elastic stiffness and low density, represent some of the lightest, stiffest and strongest materials available today. Recent advances in 3D printing and automated assembly have enabled such complicated material geometries to be fabricated at low (and declining) cost. These mechanical metamaterials have properties that are a function of their mesoscale geometry as well as their constituents, leading to combinations of properties that are unobtainable in solid materials; however, a material geometry that achieves the theoretical upper bounds for isotropic elasticity and strain energy storage (the Hashin–Shtrikman upper bounds) has yet to be identified. Here we evaluate the manner in which strain energy distributes under load in a representative selection of material geometries, to identify the morphological features associated with high elastic performance. Using finite-element models, supported by analytical methods, and a heuristic optimization scheme, we identify a material geometry that achieves the Hashin–Shtrikman upper bounds on isotropic elastic stiffness. Previous work has focused on truss networks and anisotropic honeycombs, neither of which can achieve this theoretical limit. We find that stiff but well distributed networks of plates are required to transfer loads efficiently between neighbouring members. The resulting low-density mechanical metamaterials have many advantageous properties: their mesoscale geometry can facilitate large crushing strains with high energy absorption, optical bandgaps and mechanically tunable acoustic bandgaps, high thermal insulation, buoyancy, and fluid storage and transport. Our relatively simple design can be manufactured using origami-like sheet folding and bonding methods.



Remote site-selective C–H activation directed by a catalytic bifunctional template

2017-03-08

In chemical syntheses, the activation of carbon–hydrogen (C–H) bonds converts them directly into carbon–carbon or carbon–heteroatom bonds without requiring any prior functionalization. C–H activation can thus substantially reduce the number of steps involved in a synthesis. A single specific C–H bond in a substrate can be activated by using a ‘directing’ (usually a functional) group to obtain the desired product selectively. The applicability of such a C–H activation reaction can be severely curtailed by the distance of the C–H bond in question from the directing group, and by the shape of the substrate, but several approaches have been developed to overcome these limitations. In one such approach, an understanding of the distal and geometric relationships between the functional groups and C–H bonds of a substrate has been exploited to achieve meta-selective C–H activation by using a covalently attached, U-shaped template. However, stoichiometric installation of this template has not been feasible in the absence of an appropriate functional group on which to attach it. Here we report the design of a catalytic, bifunctional nitrile template that binds a heterocyclic substrate via a reversible coordination instead of a covalent linkage. The two metal centres coordinated to this template have different roles: one reversibly anchors substrates near the catalyst, and the other cleaves remote C–H bonds. Using this strategy, we demonstrate remote, site-selective C–H olefination of heterocyclic substrates that do not have the necessary functional groups for covalently attaching templates.



Evidence for a Fe3+-rich pyrolitic lower mantle from (Al,Fe)-bearing bridgmanite elasticity data

2017-03-13

The chemical composition of Earth’s lower mantle can be constrained by combining seismological observations with mineral physics elasticity measurements. However, the lack of laboratory data for Earth’s most abundant mineral, (Mg,Fe,Al)(Al,Fe,Si)O3 bridgmanite (also known as silicate perovskite), has hampered any conclusive result. Here we report single-crystal elasticity data on (Al,Fe)-bearing bridgmanite (Mg0.9Fe0.1Si0.9Al0.1)O3 measured using high-pressure Brillouin spectroscopy and X-ray diffraction. Our measurements show that the elastic behaviour of (Al,Fe)-bearing bridgmanite is markedly different from the behaviour of the MgSiO3 endmember. We use our data to model seismic wave velocities in the top portion of the lower mantle, assuming a pyrolitic mantle composition and accounting for depth-dependent changes in iron partitioning between bridgmanite and ferropericlase. We find excellent agreement between our mineral physics predictions and the seismic Preliminary Reference Earth Model down to at least 1,200 kilometres depth, indicating chemical homogeneity of the upper and shallow lower mantle. A high Fe3+/Fe2+ ratio of about two in shallow-lower-mantle bridgmanite is required to match seismic data, implying the presence of metallic iron in an isochemical mantle. Our calculated velocities are in increasingly poor agreement with those of the lower mantle at depths greater than 1,200 kilometres, indicating either a change in bridgmanite cation ordering or a decrease in the ferric iron content of the lower mantle.



Bumblebee family lineage survival is enhanced in high-quality landscapes

2017-03-15

Insect pollinators such as bumblebees (Bombus spp.) are in global decline. A major cause of this decline is habitat loss due to agricultural intensification. A range of global and national initiatives aimed at restoring pollinator habitats and populations have been developed. However, the success of these initiatives depends critically upon understanding how landscape change affects key population-level parameters, such as survival between lifecycle stages, in target species. This knowledge is lacking for bumblebees, because of the difficulty of systematically finding and monitoring colonies in the wild. We used a combination of habitat manipulation, land-use and habitat surveys, molecular genetics and demographic and spatial modelling to analyse between-year survival of family lineages in field populations of three bumblebee species. Here we show that the survival of family lineages from the summer worker to the spring queen stage in the following year increases significantly with the proportion of high-value foraging habitat, including spring floral resources, within 250–1,000 m of the natal colony. This provides evidence for a positive impact of habitat quality on survival and persistence between successive colony cycle stages in bumblebee populations. These findings also support the idea that conservation interventions that increase floral resources at a landscape scale and throughout the season have positive effects on wild pollinators in agricultural landscapes.



KRAB zinc-finger proteins contribute to the evolution of gene regulatory networks

2017-03-08

The human genome encodes some 350 Krüppel-associated box (KRAB) domain-containing zinc-finger proteins (KZFPs), the products of a rapidly evolving gene family that has been traced back to early tetrapods. The function of most KZFPs is unknown, but a few have been demonstrated to repress transposable elements in embryonic stem (ES) cells by recruiting the transcriptional regulator TRIM28 and associated mediators of histone H3 Lys9 trimethylation (H3K9me3)-dependent heterochromatin formation and DNA methylation. Depletion of TRIM28 in human or mouse ES cells triggers the upregulation of a broad range of transposable elements, and recent data based on a few specific examples have pointed to an arms race between hosts and transposable elements as an important driver of KZFP gene selection. Here, to obtain a global view of this phenomenon, we combined phylogenetic and genomic studies to investigate the evolutionary emergence of KZFP genes in vertebrates and to identify their targets in the human genome. First, we unexpectedly reassigned the root of the family to a common ancestor of coelacanths and tetrapods. Second, although we confirmed that the majority of KZFPs bind transposable elements and pinpoint cases of ongoing co-evolution, we found that most of their transposable element targets have lost all transposition potential. Third, by examining the interplay between human KZFPs and other transcriptional modulators, we obtained evidence that KZFPs exploit evolutionarily conserved fragments of transposable elements as regulatory platforms long after the arms race against these genetic invaders has ended. Together, our results demonstrate that KZFPs partner with transposable elements to build a largely species-restricted layer of epigenetic regulation.



Phytoplankton can actively diversify their migration strategy in response to turbulent cues

2017-03-15

Marine phytoplankton inhabit a dynamic environment where turbulence, together with nutrient and light availability, shapes species fitness, succession and selection. Many species of phytoplankton are motile and undertake diel vertical migrations to gain access to nutrient-rich deeper layers at night and well-lit surface waters during the day. Disruption of this migratory strategy by turbulence is considered to be an important cause of the succession between motile and non-motile species when conditions turn turbulent. However, this classical view neglects the possibility that motile species may actively respond to turbulent cues to avoid layers of strong turbulence. Here we report that phytoplankton, including raphidophytes and dinoflagellates, can actively diversify their migratory strategy in response to hydrodynamic cues characteristic of overturning by Kolmogorov-scale eddies. Upon experiencing repeated overturning with timescales and statistics representative of ocean turbulence, an upward-swimming population rapidly (5–60 min) splits into two subpopulations, one swimming upward and one swimming downward. Quantitative morphological analysis of the harmful-algal-bloom-forming raphidophyte Heterosigma akashiwo together with a model of cell mechanics revealed that this behaviour was accompanied by a modulation of the cells’ fore–aft asymmetry. The minute magnitude of the required modulation, sufficient to invert the preferential swimming direction of the cells, highlights the advanced level of control that phytoplankton can exert on their migratory behaviour. Together with observations of enhanced cellular stress after overturning and the typically deleterious effects of strong turbulence on motile phytoplankton, these results point to an active adaptation of H. akashiwo to increase the chance of evading turbulent layers by diversifying the direction of migration within the population, in a manner suggestive of evolutionary bet-hedging. This migratory behaviour relaxes the boundaries between the fluid dynamic niches of motile and non-motile phytoplankton, and highlights that rapid responses to hydrodynamic cues are important survival strategies for phytoplankton in the ocean.



Early antibody therapy can induce long-lasting immunity to SHIV

2017-03-13

Highly potent and broadly neutralizing anti-HIV-1 antibodies (bNAbs) have been used to prevent and treat lentivirus infections in humanized mice, macaques, and humans. In immunotherapy experiments, administration of bNAbs to chronically infected animals transiently suppresses virus replication, which invariably returns to pre-treatment levels and results in progression to clinical disease. Here we show that early administration of bNAbs in a macaque simian/human immunodeficiency virus (SHIV) model is associated with very low levels of persistent viraemia, which leads to the establishment of T-cell immunity and resultant long-term infection control. Animals challenged with SHIVAD8-EO by mucosal or intravenous routes received a single 2-week course of two potent passively transferred bNAbs (3BNC117 and 10-1074 (refs 13, 14)). Viraemia remained undetectable for 56–177 days, depending on bNAb half-life in vivo. Moreover, in the 13 treated monkeys, plasma virus loads subsequently declined to undetectable levels in 6 controller macaques. Four additional animals maintained their counts of T cells carrying the CD4 antigen (CD4+) and very low levels of viraemia persisted for over 2 years. The frequency of cells carrying replication-competent virus was less than 1 per 106 circulating CD4+ T cells in the six controller macaques. Infusion of a T-cell-depleting anti-CD8β monoclonal antibody to the controller animals led to a specific decline in levels of CD8+ T cells and the rapid reappearance of plasma viraemia. In contrast, macaques treated for 15 weeks with combination anti-retroviral therapy, beginning on day 3 after infection, experienced sustained rebound plasma viraemia when treatment was interrupted. Our results show that passive immunotherapy during acute SHIV infection differs from combination anti-retroviral therapy in that it facilitates the emergence of potent CD8+ T-cell immunity able to durably suppress virus replication.



CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses

2017-03-15

The persistence of the HIV reservoir in infected individuals is a major obstacle to the development of a cure for HIV. Here, using an in vitro model of HIV-infected quiescent CD4 T cells, we reveal a gene expression signature of 103 upregulated genes that are specific for latently infected cells, including genes for 16 transmembrane proteins. In vitro screening for surface expression in HIV-infected quiescent CD4 T cells shows that the low-affinity receptor for the immunoglobulin G Fc fragment, CD32a, is the most highly induced, with no detectable expression in bystander cells. Notably, productive HIV-1 infection of T-cell-receptor-stimulated CD4 T cells is not associated with CD32a expression, suggesting that a quiescence-dependent mechanism is required for its induction. Using blood samples from HIV-1-positive participants receiving suppressive antiretroviral therapy, we identify a subpopulation of 0.012% of CD4 T cells that express CD32a and host up to three copies of HIV DNA per cell. This CD32a+ reservoir was highly enriched in inducible replication-competent proviruses and can be predominant in some participants. Our discovery that CD32a+ lymphocytes represent the elusive HIV-1 reservoir may lead to insights that will facilitate the specific targeting and elimination of this reservoir.



DND1 maintains germline stem cells via recruitment of the CCR4–NOT complex to target mRNAs

2017-03-15

The vertebrate-conserved RNA-binding protein DND1 is required for the survival of primordial germ cells (PGCs), as well as the suppression of germ cell tumours in mice. Here we show that in mice DND1 binds a UU(A/U) trinucleotide motif predominantly in the 3′ untranslated regions of mRNA, and destabilizes target mRNAs through direct recruitment of the CCR4–NOT deadenylase complex. Transcriptomic analysis reveals that the extent of suppression is dependent on the number of DND1-binding sites. This DND1-dependent mRNA destabilization is required for the survival of mouse PGCs and spermatogonial stem cells by suppressing apoptosis. The spectrum of target RNAs includes positive regulators of apoptosis and inflammation, and modulators of signalling pathways that regulate stem-cell pluripotency, including the TGFβ superfamily, all of which are aberrantly elevated in DND1-deficient PGCs. We propose that the induction of the post-transcriptional suppressor DND1 synergizes with concurrent transcriptional changes to ensure precise developmental transitions during cellular differentiation and maintenance of the germ line.



RNA m6A methylation regulates the ultraviolet-induced DNA damage response

2017-03-15

Cell proliferation and survival require the faithful maintenance and propagation of genetic information, which are threatened by the ubiquitous sources of DNA damage present intracellularly and in the external environment. A system of DNA repair, called the DNA damage response, detects and repairs damaged DNA and prevents cell division until the repair is complete. Here we report that methylation at the 6 position of adenosine (m6A) in RNA is rapidly (within 2 min) and transiently induced at DNA damage sites in response to ultraviolet irradiation. This modification occurs on numerous poly(A)+ transcripts and is regulated by the methyltransferase METTL3 (methyltransferase-like 3) and the demethylase FTO (fat mass and obesity-associated protein). In the absence of METTL3 catalytic activity, cells showed delayed repair of ultraviolet-induced cyclobutane pyrimidine adducts and elevated sensitivity to ultraviolet, demonstrating the importance of m6A in the ultraviolet-responsive DNA damage response. Multiple DNA polymerases are involved in the ultraviolet response, some of which resynthesize DNA after the lesion has been excised by the nucleotide excision repair pathway, while others participate in trans-lesion synthesis to allow replication past damaged lesions in S phase. DNA polymerase κ (Pol κ), which has been implicated in both nucleotide excision repair and trans-lesion synthesis, required the catalytic activity of METTL3 for immediate localization to ultraviolet-induced DNA damage sites. Importantly, Pol κ overexpression qualitatively suppressed the cyclobutane pyrimidine removal defect associated with METTL3 loss. Thus, we have uncovered a novel function for RNA m6A modification in the ultraviolet-induced DNA damage response, and our findings collectively support a model in which m6A RNA serves as a beacon for the selective, rapid recruitment of Pol κ to damage sites to facilitate repair and cell survival.