目次

Editorials

異常気象につながる太平洋の温度上昇を早期に捉えられるよう、観測態勢の立て直しを図るべきだ。

Support our buoys p.585

An international effort is needed to restore an early-warning system for the vast warming of the Pacific Ocean that leads to extreme weather worldwide.

doi: 10.1038/505585a

ヨーロッパが打ち出した温暖化対策の目標値は、2015年のパリ会議に向け、世界各国の努力を呼びかける合図になる。

Open invitation p.585

Europe’s proposed climate targets fire the starting gun on the long build-up to Paris 2015.

doi: 10.1038/505585b

結晶学が誕生して100年、多くの成果が上がっている。

Crystal clear p.586

Celebrating the many achievements of crystallography.

doi: 10.1038/505586a

News

韓国の幹細胞ねつ造事件の内部告発者が、8年の沈黙を破ってNatureのインタビューに。

Whistle-blower breaks his silence p.593

South Korean researcher reveals the fallout he faced from his tip-offs about former cloning fraudster Woo Suk Hwang.

doi: 10.1038/505593a

全米科学財団が閉鎖を検討しているグリーンバンク望遠鏡が、閉鎖を回避しようと、資金集めの努力を。

US struggles to offload telescopes p.594

West Virginia radio observatory seeks money from partners to fend off closure by the National Science Foundation.

doi: 10.1038/505594a

日本の研究者が、成体細胞を外部刺激のみによって再プログラム化する方法を発見。

Acid bath offers easy path to stem cells p.596

Just squeezing or bathing cells in acidic conditions can readily reprogram them into an embryonic state.

doi: 10.1038/505596a

EUの温室効果ガス削減目標に、生ぬるいと批判が。

EU climate targets under fire p.597

Critics fear that Europe’s proposed energy goals and emissions cuts are too soft.

doi: 10.1038/505597a

合成生物学企業の開発の焦点が、医薬品やバイオ燃料から、食品・フレグランスの成分などの「ファインケミカル」へ。

Synthetic-biology firms shift focus p.598

Switch to food and fragrances risks consumer rejection.

doi: 10.1038/505598a

ロシアとの関係強化を図るウクライナで、研究者たちも、EUとの関係強化を求めて反政府抗議デモの最前線に。

Ukrainian scientists in forefront of protest p.599

Researchers rally as government shuns international ties.

doi: 10.1038/505599a

News Features

結晶学:結晶の世紀

Molecular structures: The crystal century p.601

この100年、結晶学は薬の設計から火星の土壌試料の分析まで、科学の幅広い分野の進歩に役立ってきた。

doi: 10.1038/505601a

結晶学:原子の秘密

Crystallography: Atomic secrets p.602

ドイツのノーベル賞科学者ラウエによるX線回折の発見以来100年間の、結晶学のさまざまな成果を振り返る。

doi: 10.1038/505602a

結晶学:結晶学の切り札

X-ray science: The big guns p.604

強力なX線自由電子レーザー(XFEL)の開発、およびそれを利用する研究競争が世界各国で繰り広げられている。

doi: 10.1038/505604a

News & Views

フォーラム:結晶学:インスピレーションの源

Crystallography: Sources of inspiration p.620

結晶学で使われるX線源として、長い間最も多く使われてきたのはシンクロトロンである。だが、X線自由電子レーザーの登場によって競争が始まった。このフォーラムでは、シンクロトロン使用に熟達した研究者と自由電子レーザーを支持する研究者が、それぞれが「ひいき」とするX線源を構造生物学で使用する場合の見通しについて論じている。

doi: 10.1038/505620a

分子生物学:RNAが隠し持つ2層目の情報

Molecular biology: A second layer of information in RNA p.621

細胞内の全てのRNAについて、折りたたみ方を調べた3つの研究が発表された。RNAには多数の二次構造があることが分かり、その一部は細胞の機能に影響している可能性が明らかになった。

doi: 10.1038/505621a

細胞生物学:解き放たれた能力

Cell biology: Potency unchained p.622

分化した細胞が、物理的刺激を加えることで胚に似た状態に再プログラム化された。このような処理によって、胚と胎盤の両方の形成に寄与する新しい細胞集団が生じた。

doi: 10.1038/505622a

宇宙物理学:ダイナミックな隣人の肖像

Astrophysics: Portrait of a dynamic neighbour p.625

褐色矮星は、十分発達した恒星になるだけの質量を持っていない天体である。このような天体の1つの高分解能マップによって、これらの風変わりな天体の天候が非常に変わりやすいことを示すさらなる証拠が得られた。

doi: 10.1038/505625a

進化生物学:兄弟愛は雌の役に立つ

Evolutionary biology: Brotherly love benefits females p.626

交尾をめぐる雄同士の競争は、雌にとって有害な結果を招くことが多い。だが、ショウジョウバエの雄は血縁間では行動を変え、兄弟に対する場合は攻撃行動が抑制され、その結果、雌の繁殖期間が長くなることが分かった。

doi: 10.1038/nature12853

原子物理学:極を探す

Atomic physics: Polar exploration p.627

磁気単極子、つまり1個の磁荷しか持たない粒子はいまだかつて見つかったことがない。今回、こうした粒子に類似したものが、極低温のルビジウム原子雲中で生成されたことが報告された。

doi: 10.1038/505627a

Review

宇宙:小惑星帯の組成マップから導かれる太陽系の進化

Solar System evolution from compositional mapping of the asteroid belt p.629

Advances in the discovery and characterization of asteroids over the past decade have revealed an unanticipated underlying structure that points to a dramatic early history of the inner Solar System. The asteroids in the main asteroid belt have been discovered to be more compositionally diverse with size and distance from the Sun than had previously been known. This implies substantial mixing through processes such as planetary migration and the subsequent dynamical processes.

doi: 10.1038/nature12908

Articles

進化:lncRNAのレパートリーおよび発現パターンの四肢類における進化

The evolution of lncRNA repertoires and expression patterns in tetrapods p.635

Evolutionary study of long noncoding RNA (lncRNA) repertoires and expression patterns in 11 tetrapod species identifies approximately 11,000 primate-specific lncRNAs and 2,500 highly conserved lncRNAs, including approximately 400 genes that are likely to have ancient origins; many lncRNAs, particularly ancient ones, are actively regulated and may function mainly in embryonic development.

doi: 10.1038/nature12943

細胞:外界刺激が誘導する体細胞から多能性細胞への運命転換

Stimulus-triggered fate conversion of somatic cells into pluripotency p.641

One of two papers describing a reprogramming phenomenon called stimulus-triggered acquisition of pluripotency (STAP) — in STAP, lineage-committed adult somatic cells are reprogrammed to pluripotency by transient exposure to low-pH treatment, and extensive analysis of the molecular features and developmental potential of STAP cells indicates that they represent a unique state of pluripotency.

doi: 10.1038/nature12968

細胞生物学:ANP32EはクロマチンからH2A.Zを取り除くヒストンシャペロンである

ANP32E is a histone chaperone that removes H2A.Z from chromatin p.648

Human protein ANP32E is a histone chaperone that promotes removal of H2A.Z from chromatin.

doi: 10.1038/nature12922

Letters

宇宙:最近傍にある褐色矮星の全球雲マップ

A global cloud map of the nearest known brown dwarf p.654

Brown dwarfs—substellar bodies more massive than planets but not massive enough to initiate the sustained hydrogen fusion that powers self-luminous stars—are born hot and slowly cool as they age. As they cool below about 2,300 kelvin, liquid or crystalline particles composed of calcium aluminates, silicates and iron condense into atmospheric ‘dust’, which disappears at still cooler temperatures (around 1,300 kelvin). Models to explain this dust dispersal include both an abrupt sinking of the entire cloud deck into the deep, unobservable atmosphere and breakup of the cloud into scattered patches (as seen on Jupiter and Saturn). However, hitherto observations of brown dwarfs have been limited to globally integrated measurements, which can reveal surface inhomogeneities but cannot unambiguously resolve surface features. Here we report a two-dimensional map of a brown dwarf’s surface that allows identification of large-scale bright and dark features, indicative of patchy clouds. Monitoring suggests that the characteristic timescale for the evolution of global weather patterns is approximately one day.

doi: 10.1038/nature12955

原子物理学:合成磁場中でのディラック単極子の観測

Observation of Dirac monopoles in a synthetic magnetic field p.657

Magnetic monopoles—particles that behave as isolated north or south magnetic poles—have been the subject of speculation since the first detailed observations of magnetism several hundred years ago. Numerous theoretical investigations and hitherto unsuccessful experimental searches have followed Dirac’s 1931 development of a theory of monopoles consistent with both quantum mechanics and the gauge invariance of the electromagnetic field. The existence of even a single Dirac magnetic monopole would have far-reaching physical consequences, most famously explaining the quantization of electric charge. Although analogues of magnetic monopoles have been found in exotic spin ices and other systems, there has been no direct experimental observation of Dirac monopoles within a medium described by a quantum field, such as superfluid helium-3 (refs 10, 11, 12, 13). Here we demonstrate the controlled creation of Dirac monopoles in the synthetic magnetic field produced by a spinor Bose–Einstein condensate. Monopoles are identified, in both experiments and matching numerical simulations, at the termini of vortex lines within the condensate. By directly imaging such a vortex line, the presence of a monopole may be discerned from the experimental data alone. These real-space images provide conclusive and long-awaited experimental evidence of the existence of Dirac monopoles. Our result provides an unprecedented opportunity to observe and manipulate these quantum mechanical entities in a controlled environment.

doi: 10.1038/nature12954

化学:分子間クーロン脱励起によるサイト選択的およびエネルギー選択的な低速電子生成

Site- and energy-selective slow-electron production through intermolecular Coulombic decay p.661

Irradiation of matter with light tends to electronically excite atoms and molecules, with subsequent relaxation processes determining where the photon energy is ultimately deposited and electrons and ions produced. In weakly bound systems, intermolecular Coulombic decay (ICD) enables very efficient relaxation of electronic excitation through transfer of the excess energy to neighbouring atoms or molecules that then lose an electron and become ionized. Here we propose that the emission site and energy of the electrons released during this process can be controlled by coupling the ICD to a resonant core excitation. We illustrate this concept with ab initio many-body calculations on the argon–krypton model system, where resonant photoabsorption produces an initial or ‘parent’ excitation of the argon atom, which then triggers a resonant-Auger-ICD cascade that ends with the emission of a slow electron from the krypton atom. Our calculations show that the energy of the emitted electrons depends sensitively on the initial excited state of the argon atom. The incident energy can thus be adjusted both to produce the initial excitation in a chosen atom and to realize an excitation that will result in the emission of ICD electrons with desired energies. These properties of the decay cascade might have consequences for fundamental and applied radiation biology and could be of interest in the development of new spectroscopic techniques.

doi: 10.1038/nature12936

化学:分子二量体の分子間クーロン脱励起を駆動する共鳴オージェ崩壊

Resonant Auger decay driving intermolecular Coulombic decay in molecular dimers p.664

In 1997, it was predicted that an electronically excited atom or molecule placed in a loosely bound chemical system (such as a hydrogen-bonded or van-der-Waals-bonded cluster) could efficiently decay by transferring its excess energy to a neighbouring species that would then emit a low-energy electron. This intermolecular Coulombic decay (ICD) process has since been shown to be a common phenomenon, raising questions about its role in DNA damage induced by ionizing radiation, in which low-energy electrons are known to play an important part. It was recently suggested that ICD can be triggered efficiently and site-selectively by resonantly core-exciting a target atom, which then transforms through Auger decay into an ionic species with sufficiently high excitation energy to permit ICD to occur. Here we show experimentally that resonant Auger decay can indeed trigger ICD in dimers of both molecular nitrogen and carbon monoxide. By using ion and electron momentum spectroscopy to measure simultaneously the charged species created in the resonant-Auger-driven ICD cascade, we find that ICD occurs in less time than the 20 femtoseconds it would take for individual molecules to undergo dissociation. Our experimental confirmation of this process and its efficiency may trigger renewed efforts to develop resonant X-ray excitation schemes for more localized and targeted cancer radiation therapy.

doi: 10.1038/nature12927

気候:過去500~1500年間において最も低かったオーストラリアの熱帯低気圧活動

Australian tropical cyclone activity lower than at any time over the past 550–1,500 years p.667

The assessment of changes in tropical cyclone activity within the context of anthropogenically influenced climate change has been limited by the short temporal resolution of the instrumental tropical cyclone record (less than 50 years). Furthermore, controversy exists regarding the robustness of the observational record, especially before 1990. Here we show, on the basis of a new tropical cyclone activity index (CAI), that the present low levels of storm activity on the mid west and northeast coasts of Australia are unprecedented over the past 550 to 1,500 years. The CAI allows for a direct comparison between the modern instrumental record and long-term palaeotempest (prehistoric tropical cyclone) records derived from the 18O/16O ratio of seasonally accreting carbonate layers of actively growing stalagmites. Our results reveal a repeated multicentennial cycle of tropical cyclone activity, the most recent of which commenced around ad 1700. The present cycle includes a sharp decrease in activity after 1960 in Western Australia. This is in contrast to the increasing frequency and destructiveness of Northern Hemisphere tropical cyclones since 1970 in the Atlantic Ocean and the western North Pacific Ocean. Other studies project a decrease in the frequency of tropical cyclones towards the end of the twenty-first century in the southwest Pacific, southern Indian and Australian regions. Our results, although based on a limited record, suggest that this may be occurring much earlier than expected.

doi: 10.1038/nature12882

進化:ショウジョウバエでは集団内の雄の血縁性が雌への危害を低減する

Within-group male relatedness reduces harm to females in Drosophila p.672

To resolve the mechanisms that switch competition to cooperation is key to understanding biological organization. This is particularly relevant for intrasexual competition, which often leads to males harming females. Recent theory proposes that kin selection may modulate female harm by relaxing competition among male relatives. Here we experimentally manipulate the relatedness of groups of male Drosophila melanogaster competing over females to demonstrate that, as expected, within-group relatedness inhibits male competition and female harm. Females exposed to groups of three brothers unrelated to the female had higher lifetime reproductive success and slower reproductive ageing compared to females exposed to groups of three males unrelated to each other. Triplets of brothers also fought less with each other, courted females less intensively and lived longer than triplets of unrelated males. However, associations among brothers may be vulnerable to invasion by minorities of unrelated males: when two brothers were matched with an unrelated male, the unrelated male sired on average twice as many offspring as either brother. These results demonstrate that relatedness can profoundly affect fitness through its modulation of intrasexual competition, as flies plastically adjust sexual behaviour in a manner consistent with kin-selection theory.

doi: 10.1038/nature12949

細胞:多能性を獲得した再プログラム化細胞における二方向性の発生能

Bidirectional developmental potential in reprogrammed cells with acquired pluripotency p.676

We recently discovered an unexpected phenomenon of somatic cell reprogramming into pluripotent cells by exposure to sublethal stimuli, which we call stimulus-triggered acquisition of pluripotency (STAP). This reprogramming does not require nuclear transfer or genetic manipulation. Here we report that reprogrammed STAP cells, unlike embryonic stem (ES) cells, can contribute to both embryonic and placental tissues, as seen in a blastocyst injection assay. Mouse STAP cells lose the ability to contribute to the placenta as well as trophoblast marker expression on converting into ES-like stem cells by treatment with adrenocorticotropic hormone (ACTH) and leukaemia inhibitory factor (LIF). In contrast, when cultured with Fgf4, STAP cells give rise to proliferative stem cells with enhanced trophoblastic characteristics. Notably, unlike conventional trophoblast stem cells, the Fgf4-induced stem cells from STAP cells contribute to both embryonic and placental tissues in vivo and transform into ES-like cells when cultured with LIF-containing medium. Taken together, the developmental potential of STAP cells, shown by chimaera formation and in vitro cell conversion, indicates that they represent a unique state of pluripotency.

doi: 10.1038/nature12969

微生物学:ブルーストリパノソーマにおけるクオラムセンシングシグナル伝達経路の全ゲノム分析

Genome-wide dissection of the quorum sensing signalling pathway in Trypanosoma brucei p.681

The protozoan parasites Trypanosoma brucei spp. cause important human and livestock diseases in sub-Saharan Africa. In mammalian blood, two developmental forms of the parasite exist: proliferative ‘slender’ forms and arrested ‘stumpy’ forms that are responsible for transmission to tsetse flies. The slender to stumpy differentiation is a density-dependent response that resembles quorum sensing in microbial systems and is crucial for the parasite life cycle, ensuring both infection chronicity and disease transmission. This response is triggered by an elusive ‘stumpy induction factor’ (SIF) whose intracellular signalling pathway is also uncharacterized. Laboratory-adapted (monomorphic) trypanosome strains respond inefficiently to SIF but can generate forms with stumpy characteristics when exposed to cell-permeable cAMP and AMP analogues. Exploiting this, we have used a genome-wide RNA interference library screen to identify the signalling components driving stumpy formation. In separate screens, monomorphic parasites were exposed to 8-(4-chlorophenylthio)-cAMP (pCPT-cAMP) or 8-pCPT-2′-O-methyl-5′-AMP to select cells that were unresponsive to these signals and hence remained proliferative. Genome-wide Ion Torrent based RNAi target sequencing identified cohorts of genes implicated in each step of the signalling pathway, from purine metabolism, through signal transducers (kinases, phosphatases) to gene expression regulators. Genes at each step were independently validated in cells naturally capable of stumpy formation, confirming their role in density sensing in vivo. The putative RNA-binding protein, RBP7, was required for normal quorum sensing and promoted cell-cycle arrest and transmission competence when overexpressed. This study reveals that quorum sensing signalling in trypanosomes shares similarities to fundamental quiescence pathways in eukaryotic cells, its components providing targets for quorum-sensing interference-based therapeutics.

doi: 10.1038/nature12864

ウイルス進化:集団規模の塩基配列解読により明らかになったRNAウイルスの変異および適応度の全体像

Mutational and fitness landscapes of an RNA virus revealed through population sequencing p.686

RNA viruses exist as genetically diverse populations. It is thought that diversity and genetic structure of viral populations determine the rapid adaptation observed in RNA viruses and hence their pathogenesis. However, our understanding of the mechanisms underlying virus evolution has been limited by the inability to accurately describe the genetic structure of virus populations. Next-generation sequencing technologies generate data of sufficient depth to characterize virus populations, but are limited in their utility because most variants are present at very low frequencies and are thus indistinguishable from next-generation sequencing errors. Here we present an approach that reduces next-generation sequencing errors and allows the description of virus populations with unprecedented accuracy. Using this approach, we define the mutation rates of poliovirus and uncover the mutation landscape of the population. Furthermore, by monitoring changes in variant frequencies on serially passaged populations, we determined fitness values for thousands of mutations across the viral genome. Mapping of these fitness values onto three-dimensional structures of viral proteins offers a powerful approach for exploring structure–function relationships and potentially uncovering new functions. To our knowledge, our study provides the first single-nucleotide fitness landscape of an evolving RNA virus and establishes a general experimental platform for studying the genetic changes underlying the evolution of virus populations.

doi: 10.1038/nature12861

免疫:IFN誘導型遺伝子の汎ウイルス特異性はcGASの自然免疫における新規な役割を明らかにしている

Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity p.691

The type I interferon (IFN) response protects cells from viral infection by inducing hundreds of interferon-stimulated genes (ISGs), some of which encode direct antiviral effectors. Recent screening studies have begun to catalogue ISGs with antiviral activity against several RNA and DNA viruses. However, antiviral ISG specificity across multiple distinct classes of viruses remains largely unexplored. Here we used an ectopic expression assay to screen a library of more than 350 human ISGs for effects on 14 viruses representing 7 families and 11 genera. We show that 47 genes inhibit one or more viruses, and 25 genes enhance virus infectivity. Comparative analysis reveals that the screened ISGs target positive-sense single-stranded RNA viruses more effectively than negative-sense single-stranded RNA viruses. Gene clustering highlights the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS, also known as MB21D1) as a gene whose expression also broadly inhibits several RNA viruses. In vitro, lentiviral delivery of enzymatically active cGAS triggers a STING-dependent, IRF3-mediated antiviral program that functions independently of canonical IFN/STAT1 signalling. In vivo, genetic ablation of murine cGAS reveals its requirement in the antiviral response to two DNA viruses, and an unappreciated contribution to the innate control of an RNA virus. These studies uncover new paradigms for the preferential specificity of IFN-mediated antiviral pathways spanning several virus families.

doi: 10.1038/nature12862

分子生物学:in vivoでのRNA二次構造のゲノム規模プロファイリングによって明らかになった新規な調節特性

In vivo genome-wide profiling of RNA secondary structure reveals novel regulatory features p.696

RNA structure has critical roles in processes ranging from ligand sensing to the regulation of translation, polyadenylation and splicing. However, a lack of genome-wide in vivo RNA structural data has limited our understanding of how RNA structure regulates gene expression in living cells. Here we present a high-throughput, genome-wide in vivo RNA structure probing method, structure-seq, in which dimethyl sulphate methylation of unprotected adenines and cytosines is identified by next-generation sequencing. Application of this method to Arabidopsis thaliana seedlings yielded the first in vivo genome-wide RNA structure map at nucleotide resolution for any organism, with quantitative structural information across more than 10,000 transcripts. Our analysis reveals a three-nucleotide periodic repeat pattern in the structure of coding regions, as well as a less-structured region immediately upstream of the start codon, and shows that these features are strongly correlated with translation efficiency. We also find patterns of strong and weak secondary structure at sites of alternative polyadenylation, as well as strong secondary structure at 5′ splice sites that correlates with unspliced events. Notably, in vivo structures of messenger RNAs annotated for stress responses are poorly predicted in silico, whereas mRNA structures of genes related to cell function maintenance are well predicted. Global comparison of several structural features between these two categories shows that the mRNAs associated with stress responses tend to have more single-strandedness, longer maximal loop length and higher free energy per nucleotide, features that may allow these RNAs to undergo conformational changes in response to environmental conditions. Structure-seq allows the RNA structurome and its biological roles to be interrogated on a genome-wide scale and should be applicable to any organism.

doi: 10.1038/nature12756

分子生物学:RNA構造の全ゲノム探索によって明らかになったin vivoでのmRNA構造の能動的解きほぐし

Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo p.701

RNA has a dual role as an informational molecule and a direct effector of biological tasks. The latter function is enabled by RNA’s ability to adopt complex secondary and tertiary folds and thus has motivated extensive computational and experimental efforts for determining RNA structures. Existing approaches for evaluating RNA structure have been largely limited to in vitro systems, yet the thermodynamic forces which drive RNA folding in vitro may not be sufficient to predict stable RNA structures in vivo. Indeed, the presence of RNA-binding proteins and ATP-dependent helicases can influence which structures are present inside cells. Here we present an approach for globally monitoring RNA structure in native conditions in vivo with single-nucleotide precision. This method is based on in vivo modification with dimethyl sulphate (DMS), which reacts with unpaired adenine and cytosine residues, followed by deep sequencing to monitor modifications. Our data from yeast and mammalian cells are in excellent agreement with known messenger RNA structures and with the high-resolution crystal structure of the Saccharomyces cerevisiae ribosome. Comparison between in vivo and in vitro data reveals that in rapidly dividing cells there are vastly fewer structured mRNA regions in vivo than in vitro. Even thermostable RNA structures are often denatured in cells, highlighting the importance of cellular processes in regulating RNA structure. Indeed, analysis of mRNA structure under ATP-depleted conditions in yeast shows that energy-dependent processes strongly contribute to the predominantly unfolded state of mRNAs inside cells. Our studies broadly enable the functional analysis of physiological RNA structures and reveal that, in contrast to the Anfinsen view of protein folding whereby the structure formed is the most thermodynamically favourable, thermodynamics have an incomplete role in determining mRNA structure in vivo.

doi: 10.1038/nature12894

分子生物学:ヒトのトランスクリプトーム全体におけるRNA二次構造の状態と変動

Landscape and variation of RNA secondary structure across the human transcriptome p.706

In parallel to the genetic code for protein synthesis, a second layer of information is embedded in all RNA transcripts in the form of RNA structure. RNA structure influences practically every step in the gene expression program. However, the nature of most RNA structures or effects of sequence variation on structure are not known. Here we report the initial landscape and variation of RNA secondary structures (RSSs) in a human family trio (mother, father and their child). This provides a comprehensive RSS map of human coding and non-coding RNAs. We identify unique RSS signatures that demarcate open reading frames and splicing junctions, and define authentic microRNA-binding sites. Comparison of native deproteinized RNA isolated from cells versus refolded purified RNA suggests that the majority of the RSS information is encoded within RNA sequence. Over 1,900 transcribed single nucleotide variants (approximately 15% of all transcribed single nucleotide variants) alter local RNA structure. We discover simple sequence and spacing rules that determine the ability of point mutations to impact RSSs. Selective depletion of ‘riboSNitches’ versus structurally synonymous variants at precise locations suggests selection for specific RNA shapes at thousands of sites, including 3′ untranslated regions, binding sites of microRNAs and RNA-binding proteins genome-wide. These results highlight the potentially broad contribution of RNA structure and its variation to gene regulation.

doi: 10.1038/nature12946

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