目次

Editorials

ヒトパピローマウイルス(HPV)ワクチンの接種を、積極的に進めるべきだ。

Active protection p.253

Parents should vaccinate their children against human papillomavirus.

doi: 10.1038/499253b

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米国とヨーロッパの大規模な2つの脳研究計画は、神経科学を大変革する可能性を秘めているが、他の脳研究の資金を奪わない配慮が必要だ。

The benefits of brain mapping p.253

Two huge projects have the potential to revolutionize neuroscience, as long as they don’t drain money from other work and are monitored to keep them on target.

doi: 10.1038/499253a

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レーザーを利用すれば、宇宙船からのデータ転送の効率が大幅に改善するが、その実現には、まだ克服すべき課題がある。

Light show p.254

Lasers will one day improve data transfer from spacecraft, but hurdles must still be overcome.

doi: 10.1038/499254a

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News

小惑星からの岩石採取を目指すNASAの探査計画が、目標探しで足踏み。

Asteroid plan looks rocky p.261

NASA mission to retrieve a small space rock could be tripped up by lack of candidates.

doi: 10.1038/499261a

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米オレゴン州の畑で未認可遺伝子組換え(GM)コムギが見つかり、侵入経路の調査が。

Hunt for mystery GM wheat hots up p.262

Investigators hope to track origins of the transgenic crop.

doi: 10.1038/499262a

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NIHが、開発中止になった新薬候補を、別の用途で再開発する研究を推進へ。

NIH gambles on recycled drugs p.263

Early success could bolster congressional support for agency’s translational science centre.

doi: 10.1038/499263a

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牛疫の根絶後、一時的に禁止されていた牛疫ウイルスの研究が、厳しい管理の下で再開へ。

Rinderpest research restarts p.264

As moratorium lifts, oversight is put in place to assess studies on eradicated cattle virus.

doi: 10.1038/499264a

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福島は、放射能の生態系への影響を調べられる貴重な場だが、資金の不足も。

Fukushima offers real-time ecolab p.265

But ecologists say they need more funding.

doi: 10.1038/499265a

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惑星科学のビッグデータの活用に向け、レーザーによるデータ転送に期待が。

Lasers boost space communications p.266

Optical systems set to handle planetary science’s big data.

doi: 10.1038/499266a

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News Features

デジタル学習:仮想研究室

Education online: The virtual lab p.268

オンライン学習の爆発的人気を受けて、科学の実践的技術を教える新しい方法を編み出そうと研究が行われている。

doi: 10.1038/499268a

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神経科学:脳の謎を解く

Neuroscience: Solving the brain p.272

米国とヨーロッパがそれぞれ、脳の働きを理解すべく数十億ドル規模の大プロジェクトを計画しているが、技術的な課題は大きい。

doi: 10.1038/499272a

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News & Views

量子物理学:次の段階に進んだアンドレーエフ状態

Quantum physics: Andreev states taken to the next level p.286

アンドレーエフ束縛状態は超伝導の弱結合理論の特徴である。用途の広いジョセフソン効果をソース、デバイス、検出器として使って、このような1/2スピン状態が直接観測された。

doi: 10.1038/499286a

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生物地球化学:森林での二酸化炭素と水の使われ方

Biogeochemistry: Carbon dioxide and water use in forests p.287

植物は大気中に含まれる二酸化炭素の濃度の上昇に、水をより効率的に使うことで対処すると予想されている。この仮説を直接裏付ける証拠が森林での観察から得られたが、効果の大きさについては論争を呼びそうだ。

doi: 10.1038/nature12411

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RNA生物物理学:3状態のバランスをとる

RNA biophysics: A three-state balancing act p.289

病原体が温度変化を生き抜く仕組みはどのようなものなのだろうか。分子レベルで見ると、ある細菌は、該当するRNAの塩基配列の構造平衡を介して、温度に応じた遺伝子発現の調節を行うらしい。

doi: 10.1038/nature12410

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素粒子物理学:レット・イット・B

Particle physics: Let it B p.290

CP対称性の破れとして知られる現象は、物質の存在をまさに説明するもので、BS0中間子の崩壊で観測された。この知見は素粒子物理学の標準模型が正しいことをまた別の側面から示している。

doi: 10.1038/499290a

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がん:計算された治療

Cancer: Calculated treatment p.291

患者のデータと関連付けられた数値モデリングで、がんにおける薬剤耐性の発生防止には併用療法の方が連続療法よりも効果的であることが示唆されている。この予測手法は個別化治療への道を容易にする可能性がある。

doi: 10.1038/499291a

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細菌学:縦に並んだ毒素

Bacteriology: Toxins in tandem p.293

腸チフス菌(Salmonella Typhi)が産生する毒素の分析によって、毒素サブユニットが異例の構造をとっていることが明らかになり、腸チフスの症状の大半が片方のサブユニットのDNA損傷能に関連していることも分かった。

doi: 10.1038/nature12409

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Articles

神経科学:ニューロン活動を画像化するための超高感度蛍光タンパク質

Ultrasensitive fluorescent proteins for imaging neuronal activity p.295

Sensitive protein sensors of calcium have been created; these new tools are shown to report neural activity in cultured neurons, flies and zebrafish and can detect single action potentials and synaptic activation in the mouse visual cortex in vivo.

doi: 10.1038/nature12354

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発生:膜に存在するmyomakerは筋芽細胞融合と筋形成の活性化物質である

Myomaker is a membrane activator of myoblast fusion and muscle formation p.301

A muscle-specific membrane protein called myomaker is transiently expressed during myogenesis and is both necessary and sufficient to drive myoblast fusion in vivo and in vitro.

doi: 10.1038/nature12343

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細胞:LRG1は内皮でのTGF-βシグナル伝達の調整により血管新生を促進する

LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling p.306

LRG1 is identified as a new regulator of TGF-β signalling that promotes angiogenesis via a TβRII–ALK1–ENG–Smad1/5/8 signalling pathway; antibody-mediated inhibition of LRG1 reduces pathogenic neovascularization in a mouse model of retinal injury.

doi: 10.1038/nature12345

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Letters

物理:超伝導原子接触においてアンドレーエフ対を励起する

Exciting Andreev pairs in a superconducting atomic contact p.312

The Josephson effect describes the flow of supercurrent in a weak link—such as a tunnel junction, nanowire or molecule—between two superconductors. It is the basis for a variety of circuits and devices, with applications ranging from medicine to quantum information. Experiments using Josephson circuits that behave like artificial atoms are now revolutionizing the way we probe and exploit the laws of quantum physics. Microscopically, the supercurrent is carried by Andreev pair states, which are localized at the weak link. These states come in doublets and have energies inside the superconducting gap. Existing Josephson circuits are based on properties of just the ground state of each doublet, and so far the excited states have not been directly detected. Here we establish their existence through spectroscopic measurements of superconducting atomic contacts. The spectra, which depend on the atomic configuration and on the phase difference between the superconductors, are in complete agreement with theory. Andreev doublets could be exploited to encode information in novel types of superconducting qubits.

doi: 10.1038/nature12315

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材料:高性能ペロブスカイト増感太陽電池を得る手段としての逐次析出

Sequential deposition as a route to high-performance perovskite-sensitized solar cells p.316

Following pioneering work, solution-processable organic–inorganic hybrid perovskites—such as CH3NH3PbX3 (X = Cl, Br, I)—have attracted attention as light-harvesting materials for mesoscopic solar cells. So far, the perovskite pigment has been deposited in a single step onto mesoporous metal oxide films using a mixture of PbX2 and CH3NH3X in a common solvent. However, the uncontrolled precipitation of the perovskite produces large morphological variations, resulting in a wide spread of photovoltaic performance in the resulting devices, which hampers the prospects for practical applications. Here we describe a sequential deposition method for the formation of the perovskite pigment within the porous metal oxide film. PbI2 is first introduced from solution into a nanoporous titanium dioxide film and subsequently transformed into the perovskite by exposing it to a solution of CH3NH3I. We find that the conversion occurs within the nanoporous host as soon as the two components come into contact, permitting much better control over the perovskite morphology than is possible with the previously employed route. Using this technique for the fabrication of solid-state mesoscopic solar cells greatly increases the reproducibility of their performance and allows us to achieve a power conversion efficiency of approximately 15 per cent (measured under standard AM1.5G test conditions on solar zenith angle, solar light intensity and cell temperature). This two-step method should provide new opportunities for the fabrication of solution-processed photovoltaic cells with unprecedented power conversion efficiencies and high stability equal to or even greater than those of today’s best thin-film photovoltaic devices.

doi: 10.1038/nature12340

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生物無機化学:ハロゲナーゼSyrB2の触媒サイクルにおけるFe(IV)=O中間体の解明

Elucidation of the Fe(iv)=O intermediate in the catalytic cycle of the halogenase SyrB2 p.320

Mononuclear non-haem iron (NHFe) enzymes catalyse a broad range of oxidative reactions, including halogenation, hydroxylation, ring closure, desaturation and aromatic ring cleavage reactions. They are involved in a number of biological processes, including phenylalanine metabolism, the production of neurotransmitters, the hypoxic response and the biosynthesis of secondary metabolites. The reactive intermediate in the catalytic cycles of these enzymes is a high-spin S = 2 Fe(iv)=O species, which has been trapped for a number of NHFe enzymes, including the halogenase SyrB2 (syringomycin biosynthesis enzyme 2). Computational studies aimed at understanding the reactivity of this Fe(iv)=O intermediate are limited in applicability owing to the paucity of experimental knowledge about its geometric and electronic structure. Synchrotron-based nuclear resonance vibrational spectroscopy (NRVS) is a sensitive and effective method that defines the dependence of the vibrational modes involving Fe on the nature of the Fe(iv)=O active site. Here we present NRVS structural characterization of the reactive Fe(iv)=O intermediate of a NHFe enzyme, namely the halogenase SyrB2 from the bacterium Pseudomonas syringae pv. syringae. This intermediate reacts via an initial hydrogen-atom abstraction step, performing subsequent halogenation of the native substrate or hydroxylation of non-native substrates. A correlation of the experimental NRVS data to electronic structure calculations indicates that the substrate directs the orientation of the Fe(iv)=O intermediate, presenting specific frontier molecular orbitals that can activate either selective halogenation or hydroxylation.

doi: 10.1038/nature12304

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地球:大気中二酸化炭素濃度の増加に伴う森林の水利用効率の上昇

Increase in forest water-use efficiency as atmospheric carbon dioxide concentrations rise p.324

Terrestrial plants remove CO2 from the atmosphere through photosynthesis, a process that is accompanied by the loss of water vapour from leaves. The ratio of water loss to carbon gain, or water-use efficiency, is a key characteristic of ecosystem function that is central to the global cycles of water, energy and carbon. Here we analyse direct, long-term measurements of whole-ecosystem carbon and water exchange. We find a substantial increase in water-use efficiency in temperate and boreal forests of the Northern Hemisphere over the past two decades. We systematically assess various competing hypotheses to explain this trend, and find that the observed increase is most consistent with a strong CO2 fertilization effect. The results suggest a partial closure of stomata—small pores on the leaf surface that regulate gas exchange—to maintain a near-constant concentration of CO2 inside the leaf even under continually increasing atmospheric CO2 levels. The observed increase in forest water-use efficiency is larger than that predicted by existing theory and 13 terrestrial biosphere models. The increase is associated with trends of increasing ecosystem-level photosynthesis and net carbon uptake, and decreasing evapotranspiration. Our findings suggest a shift in the carbon- and water-based economics of terrestrial vegetation, which may require a reassessment of the role of stomatal control in regulating interactions between forests and climate change, and a re-evaluation of coupled vegetation–climate models.

doi: 10.1038/nature12291

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地球:ケイ酸塩地球のS、Se、Te比が必要とする揮発性物質に富むレイトベニア

Ratios of S, Se and Te in the silicate Earth require a volatile-rich late veneer p.328

The excess of highly siderophile (iron-loving) elements (HSEs) and the chondritic ratios of most HSEs in the bulk silicate Earth (BSE) may reflect the accretion of a chondritic ‘late veneer’ of about 0.5 per cent of Earth’s mass after core formation. The amount of volatiles contained in the late veneer is a key constraint on the budget and the origin of the volatiles in Earth. At high pressures and temperatures, the moderately volatile chalcogen elements sulphur (S), selenium (Se) and tellurium (Te) are moderately to highly siderophile; thus, if depleted by core formation their mantle abundances should reflect the volatile composition of the late veneer. Here we report ratios and abundances of S, Se and Te in the mantle determined from new isotope dilution data for post-Archaean mantle peridotites. The mean S/Se and Se/Te ratios of mantle lherzolites overlap with CI (Ivuna-type) carbonaceous chondrite values. The Se/Te ratios of ordinary and enstatite chondrites are significantly different. The chalcogen/HSE ratio of the BSE is similar to that of CM (Mighei-type) carbonaceous chondrites, consistent with the view that the HSE signature of the BSE reflects a predominance of slightly volatile-depleted, carbonaceous-chondrite-like material, possibly with a minor proportion of non-chondritic material. Depending on the estimates for the abundances of water and carbon in the BSE, the late veneer may have supplied 20 to 100 per cent of the budget of hydrogen and carbon in the BSE.

doi: 10.1038/nature12285

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進化:ショウジョウバエで起こった祖先の性染色体から常染色体への逆戻り

Reversal of an ancient sex chromosome to an autosome in Drosophila p.332

Although transitions of sex-determination mechanisms are frequent in species with homomorphic sex chromosomes, heteromorphic sex chromosomes are thought to represent a terminal evolutionary stage owing to chromosome-specific adaptations such as dosage compensation or an accumulation of sex-specific mutations. Here we show that an autosome of Drosophila, the dot chromosome, was ancestrally a differentiated X chromosome. We analyse the whole genome of true fruitflies (Tephritidae), flesh flies (Sarcophagidae) and soldier flies (Stratiomyidae) to show that genes located on the dot chromosome of Drosophila are X-linked in outgroup species, whereas Drosophila X-linked genes are autosomal. We date this chromosomal transition to early drosophilid evolution by sequencing the genome of other Drosophilidae. Our results reveal several puzzling aspects of Drosophila dot chromosome biology to be possible remnants of its former life as a sex chromosome, such as its minor feminizing role in sex determination or its targeting by a chromosome-specific regulatory mechanism. We also show that patterns of biased gene expression of the dot chromosome during early embryogenesis, oogenesis and spermatogenesis resemble that of the current X chromosome. Thus, although sex chromosomes are not necessarily evolutionary end points and can revert back to an autosomal inheritance, the highly specialized genome architecture of this former X chromosome suggests that severe fitness costs must be overcome for such a turnover to occur.

doi: 10.1038/nature12235

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神経科学:体性感覚皮質の長距離投射ニューロンの行動依存的な動員

Behaviour-dependent recruitment of long-range projection neurons in somatosensory cortex p.336

In the mammalian neocortex, segregated processing streams are thought to be important for forming sensory representations of the environment, but how local information in primary sensory cortex is transmitted to other distant cortical areas during behaviour is unclear. Here we show task-dependent activation of distinct, largely non-overlapping long-range projection neurons in the whisker region of primary somatosensory cortex (S1) in awake, behaving mice. Using two-photon calcium imaging, we monitored neuronal activity in anatomically identified S1 neurons projecting to secondary somatosensory (S2) or primary motor (M1) cortex in mice using their whiskers to perform a texture-discrimination task or a task that required them to detect the presence of an object at a certain location. Whisking-related cells were found among S2-projecting (S2P) but not M1-projecting (M1P) neurons. A higher fraction of S2P than M1P neurons showed touch-related responses during texture discrimination, whereas a higher fraction of M1P than S2P neurons showed touch-related responses during the detection task. In both tasks, S2P and M1P neurons could discriminate similarly between trials producing different behavioural decisions. However, in trials producing the same decision, S2P neurons performed better at discriminating texture, whereas M1P neurons were better at discriminating location. Sensory stimulus features alone were not sufficient to elicit these differences, suggesting that selective transmission of S1 information to S2 and M1 is driven by behaviour.

doi: 10.1038/nature12236

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神経科学:ニューロン活動依存的なMeCP2のスレオニン308リン酸化はNCoRとの相互作用を調節する

Activity-dependent phosphorylation of MeCP2 threonine 308 regulates interaction with NCoR p.341

Rett syndrome (RTT) is an X-linked human neurodevelopmental disorder with features of autism and severe neurological dysfunction in females. RTT is caused by mutations in methyl-CpG-binding protein 2 (MeCP2), a nuclear protein that, in neurons, regulates transcription, is expressed at high levels similar to that of histones, and binds to methylated cytosines broadly across the genome. By phosphotryptic mapping, we identify three sites (S86, S274 and T308) of activity-dependent MeCP2 phosphorylation. Phosphorylation of these sites is differentially induced by neuronal activity, brain-derived neurotrophic factor, or agents that elevate the intracellular level of 3′,5′-cyclic AMP (cAMP), indicating that MeCP2 may function as an epigenetic regulator of gene expression that integrates diverse signals from the environment. Here we show that the phosphorylation of T308 blocks the interaction of the repressor domain of MeCP2 with the nuclear receptor co-repressor (NCoR) complex and suppresses the ability of MeCP2 to repress transcription. In knock-in mice bearing the common human RTT missense mutation R306C, neuronal activity fails to induce MeCP2 T308 phosphorylation, suggesting that the loss of T308 phosphorylation might contribute to RTT. Consistent with this possibility, the mutation of MeCP2 T308A in mice leads to a decrease in the induction of a subset of activity-regulated genes and to RTT-like symptoms. These findings indicate that the activity-dependent phosphorylation of MeCP2 at T308 regulates the interaction of MeCP2 with the NCoR complex, and that RTT in humans may be due, in part, to the loss of activity-dependent MeCP2 T308 phosphorylation and a disruption of the phosphorylation-regulated interaction of MeCP2 with the NCoR complex.

doi: 10.1038/nature12348

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医学:ハダカデバネズミのがん抵抗性には、高分子量ヒアルロナンが関わっている

High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat p.346

The naked mole rat (Heterocephalus glaber) displays exceptional longevity, with a maximum lifespan exceeding 30 years. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years. In addition to their longevity, naked mole rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer. Here we identify a mechanism responsible for the naked mole rat’s cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high-molecular-mass hyaluronan (HA), which is over five times larger than human or mouse HA. This high-molecular-mass HA accumulates abundantly in naked mole-rat tissues owing to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signalling, as they have a higher affinity to HA compared with mouse or human cells. Perturbation of the signalling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high-molecular-mass HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, HYAL2, naked mole-rat cells become susceptible to malignant transformation and readily form tumours in mice. We speculate that naked mole rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species.

doi: 10.1038/nature12234

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医学:チフス菌のA2B5キメラ型毒素の構造と機能

Structure and function of the Salmonella Typhi chimaeric A2B5 typhoid toxin p.350

Salmonella enterica serovar Typhi (S. Typhi) differs from most other salmonellae in that it causes a life-threatening systemic infection known as typhoid fever. The molecular bases for its unique clinical presentation are unknown. Here we find that the systemic administration of typhoid toxin, a unique virulence factor of S. Typhi, reproduces many of the acute symptoms of typhoid fever in an animal model. We identify specific carbohydrate moieties on specific surface glycoproteins that serve as receptors for typhoid toxin, which explains its broad cell target specificity. We present the atomic structure of typhoid toxin, which shows an unprecedented A2B5 organization with two covalently linked A subunits non-covalently associated to a pentameric B subunit. The structure provides insight into the toxin’s receptor-binding specificity and delivery mechanisms and reveals how the activities of two powerful toxins have been co-opted into a single, unique toxin that can induce many of the symptoms characteristic of typhoid fever. These findings may lead to the development of potentially life-saving therapeutics against typhoid fever.

doi: 10.1038/nature12377

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生物物理:3状態機構が、リボスイッチのリガンドと温度感知とを共役させている

Three-state mechanism couples ligand and temperature sensing in riboswitches p.355

Riboswitches are cis-acting gene-regulatory RNA elements that can function at the level of transcription, translation and RNA cleavage. The commonly accepted molecular mechanism for riboswitch function proposes a ligand-dependent conformational switch between two mutually exclusive states. According to this mechanism, ligand binding to an aptamer domain induces an allosteric conformational switch of an expression platform, leading to activation or repression of ligand-related gene expression. However, many riboswitch properties cannot be explained by a pure two-state mechanism. Here we show that the regulation mechanism of the adenine-sensing riboswitch, encoded by the add gene on chromosome II of the human Gram-negative pathogenic bacterium Vibrio vulnificus, is notably different from a two-state switch mechanism in that it involves three distinct stable conformations. We characterized the temperature and Mg2+ dependence of the population ratios of the three conformations and the kinetics of their interconversion at nucleotide resolution. The observed temperature dependence of a pre-equilibrium involving two structurally distinct ligand-free conformations of the add riboswitch conferred efficient regulation over a physiologically relevant temperature range. Such robust switching is a key requirement for gene regulation in bacteria that have to adapt to environments with varying temperatures. The translational adenine-sensing riboswitch represents the first example, to our knowledge, of a temperature-compensated regulatory RNA element.

doi: 10.1038/nature12378

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分子生物学:プロモーターの方向性はU1 snRNPとポリアデニル化シグナルによって制御される

Promoter directionality is controlled by U1 snRNP and polyadenylation signals p.360

Transcription of the mammalian genome is pervasive, but productive transcription outside of protein-coding genes is limited by unknown mechanisms. In particular, although RNA polymerase II (RNAPII) initiates divergently from most active gene promoters, productive elongation occurs primarily in the sense-coding direction. Here we show in mouse embryonic stem cells that asymmetric sequence determinants flanking gene transcription start sites control promoter directionality by regulating promoter-proximal cleavage and polyadenylation. We find that upstream antisense RNAs are cleaved and polyadenylated at poly(A) sites (PASs) shortly after initiation. De novo motif analysis shows PAS signals and U1 small nuclear ribonucleoprotein (snRNP) recognition sites to be the most depleted and enriched sequences, respectively, in the sense direction relative to the upstream antisense direction. These U1 snRNP sites and PAS sites are progressively gained and lost, respectively, at the 5′ end of coding genes during vertebrate evolution. Functional disruption of U1 snRNP activity results in a dramatic increase in promoter-proximal cleavage events in the sense direction with slight increases in the antisense direction. These data suggest that a U1–PAS axis characterized by low U1 snRNP recognition and a high density of PASs in the upstream antisense region reinforces promoter directionality by promoting early termination in upstream antisense regions, whereas proximal sense PAS signals are suppressed by U1 snRNP. We propose that the U1–PAS axis limits pervasive transcription throughout the genome.

doi: 10.1038/nature12349

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構造生物学:X線結晶解析により明らかとなったマルトース輸送体での炭素カタボライト抑制

Carbon catabolite repression of the maltose transporter revealed by X-ray crystallography p.364

Efficient carbon utilization is critical to the survival of microorganisms in competitive environments. To optimize energy usage, bacteria have developed an integrated control system to preferentially uptake carbohydrates that support rapid growth. The availability of a preferred carbon source, such as glucose, represses the synthesis and activities of proteins necessary for the transport and metabolism of secondary carbon sources. This regulatory phenomenon is defined as carbon catabolite repression. In enteric bacteria, the key player of carbon catabolite repression is a component of the glucose-specific phosphotransferase system, enzyme IIA (EIIAGlc). It is known that unphosphorylated EIIAGlc binds to and inhibits a variety of transporters when glucose is available. However, understanding the underlying molecular mechanism has been hindered by the complete absence of structures for any EIIAGlc–transporter complexes. Here we present the 3.9 Å crystal structure of Escherichia coli EIIAGlc in complex with the maltose transporter, an ATP-binding cassette (ABC) transporter. The structure shows that two EIIAGlc molecules bind to the cytoplasmic ATPase subunits, stabilizing the transporter in an inward-facing conformation and preventing the structural rearrangements necessary for ATP hydrolysis. We also show that the half-maximal inhibitory concentrations of the full-length EIIAGlc and an amino-terminal truncation mutant differ by 60-fold, consistent with the hypothesis that the amino-terminal region, disordered in the crystal structure, functions as a membrane anchor to increase the effective EIIAGlc concentration at the membrane. Together these data suggest a model of how the central regulatory protein EIIAGlc allosterically inhibits maltose uptake in E. coli.

doi: 10.1038/nature12232

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