目次

Editorial

女性の科学界での活躍をいまだに阻んでいる原因を考え、抜本的な解決に取り組むべきときだ。

Science for all p.5

Many women are deterred from pursuing a career in science at the highest levels. Much more must be done to address the reasons behind this potential waste of human talent.

doi: 10.1038/495005a

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News

米西海岸で、東日本大震災の漂着物による生物種の侵入に懸念が。

Tsunami triggers invasion concerns p.13

Biologists track species on flotsam from Japan to US shores.

doi: 10.1038/495013a

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欧州の次期地球探査計画は、観測対象の絞り込みが難しい課題に。

ESA’s climate-eye dilemma p.15

Scientists face difficult choice for Europe’s next Earth-observation mission.

doi: 10.1038/495015a

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ロシアのチェバルクリ隕石落下の詳細が次第に明らかに。

The death of the Chebarkul meteor p.16

Scientists reconstruct a battered traveller’s final moments.

doi: 10.1038/495016a

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絶縁体から導体へと転移する金属酸化物を用いた、新しいトランジスターに期待が。

Metal oxide chips show promise p.17

Materials that flip from insulator to conductor could make energy-efficient transistors.

doi: 10.1038/495017a

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商業用ロケットの主導権争いが熾烈に。

Commercial space race heats up p.18

Antares test could challenge dominance of Falcon 9 rocket.

doi: 10.1038/495018a

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脳活動の解明を目指す壮大な計画の陰で、ほかの研究へのしわ寄せを懸念する声も。

Behind the scenes of a brain-mapping moon shot p.19

Critics fear that a proposed megaproject could crowd out other biological research.

doi: 10.1038/495019a

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News Features

女性の仕事

Women in science: Women's work p.21

科学分野での男女平等を実現するには、まだ多くの課題が残されている。

doi: 10.1038/495021a

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気になるジェンダー・ギャップ

Inequality quantified: Mind the gender gap p.22

改善されてはいるものの、女性科学者はいまだに、差別、低報酬、助成の不平などに悩まされている。

doi: 10.1038/495022a

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役員室からの締め出し

Women in biotechnology: Barred from the boardroom p.25

科学研究に携わる女性は増えているが、業界や審議会はいまだに男性が牛耳っている。

doi: 10.1038/495025a

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科学界の「サーティー・サムシング」

From the frontline: 30 something science p.28

「女だからってそんなの関係ない」と、研究と子育てを両立させる気鋭の30代女性科学者たちは語る。

doi: 10.1038/495028a

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News & Views

バイオテクノロジー:ゲノムを書き直す

Biotechnology: Rewriting a genome p.50

ガイドRNA分子を使ってDNA標的を切断する細菌酵素が、細菌やヒトの細胞のゲノムからゼブラフィッシュのような個体のゲノムまで、部位特異的修飾をするためのプログラム可能な手段として広く使われるようになった。

doi: 10.1038/495050a

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宇宙物理学:最も近い銀河までの正確な距離

Astrophysics: An accurate distance to the nearest galaxy p.51

大マゼラン雲までの距離の非常に正確な値が得られれば、宇宙の「暗黒エネルギー」について、天文学上のよりよい物差しが得られる。今回、連星系を使うことで、2.2%という精度での値が得られた。

doi: 10.1038/495051a

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幹細胞:陰窩についての統一理論

Stem Cells: A unifying theory for the crypt p.53

腸の陰窩構造に局在していて静止状態にある細胞が幹細胞かどうかということは、ずっと不明確なままだった。この問題の答えは、幹細胞という言葉が何を意味しているかによってイエスでもありノーでもあるようだ。

doi: 10.1038/nature11958

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触媒作用:メタノール経済社会へ一歩接近

Catalysis: A step closer to a methanol economy p.54

数ppmの濃度で、大量に得られる単純な化学製品のメタノールから水素ガスを放出させるルテニウム触媒が開発された。この進歩によって、メタノールを自動車燃料用の水素ガス供給源として使うことが可能になるかもしれない。

doi: 10.1038/nature11955

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神経科学:さえずりの構成単位

Neuroscience: The units of a song p.56

鳥のさえずりが作り出される際に、運動を計画するニューロンがどの時点で働くのかについては議論が続いている。新しいデータからは、このようなニューロンの急激な活動が発声器官への命令に突然の変化をもたらすと考えられる。

doi: 10.1038/nature11957

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細胞生物学:「過ぎたるは及ばざるがごとし」という教訓

Cell biology: A fable of too much too fast p.57

ある種の細菌と菌類の1つは共に、概日時計タンパク質の産生を最適化できないような遺伝子塩基配列を使っている。別々に行われた2つの研究では、産生されるタンパク質の量を減らすことの利点について、異なる説明が与えられている。

doi: 10.1038/nature11952

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Articles

神経科学:基本的ジェスチャー動態はさえずり前運動皮質ニューロンにより符号化される

Elemental gesture dynamics are encoded by song premotor cortical neurons p.59

The auditory response of song premotor HVC neurons in sleeping birds, and HVC activity in singing birds, is synchronized with particular moments of vocal motor movements as defined by a dynamical systems model of song production; this HVC activity could be used as a ‘forward’ model to predict behaviour and evaluate feedback.

doi: 10.1038/nature11967

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細胞:腸のラベル保持細胞は、Lgr5を発現する分泌系前駆細胞である

Intestinal label-retaining cells are secretory precursors expressing Lgr5 p.65

A new method to trace the lineage of slow cycling label-retaining cells (LRCs) in vivo identifies a population of LRCs that have features of committed Paneth cells but still express stem-cell markers such as Lgr5; the slow cycling cells differentiate into Paneth cells without cell division, but after injury can also repopulate the stem-cell niche and contribute to the regeneration of all intestinal lineages.

doi: 10.1038/nature11965

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構造生物学:11個のサブユニットからなる真核生物エキソソーム複合体のRNAが結合した状態の結晶構造

Crystal structure of an RNA-bound 11-subunit eukaryotic exosome complex p.70

The crystal structure of a complete yeast exosome (Exo-10) bound to a region of the Rrp6 nuclease and an RNA substrate is determined, demonstrating that the exosome binds and degrades RNA molecules with a channelling mechanism that is largely conserved in all kingdoms of life and is similar to the mechanism used by the proteasome to degrade polypeptides.

doi: 10.1038/nature11870

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Letters

宇宙:食連星による大マゼラン雲までの2%の精度での距離計測

An eclipsing-binary distance to the Large Magellanic Cloud accurate to two per cent p.76

In the era of precision cosmology, it is essential to determine the Hubble constant to an accuracy of three per cent or better. At present, its uncertainty is dominated by the uncertainty in the distance to the Large Magellanic Cloud (LMC), which, being our second-closest galaxy, serves as the best anchor point for the cosmic distance scale. Observations of eclipsing binaries offer a unique opportunity to measure stellar parameters and distances precisely and accurately. The eclipsing-binary method was previously applied to the LMC, but the accuracy of the distance results was lessened by the need to model the bright, early-type systems used in those studies. Here we report determinations of the distances to eight long-period, late-type eclipsing systems in the LMC, composed of cool, giant stars. For these systems, we can accurately measure both the linear and the angular sizes of their components and avoid the most important problems related to the hot, early-type systems. The LMC distance that we derive from these systems (49.97 ± 0.19 (statistical) ± 1.11 (systematic) kiloparsecs) is accurate to 2.2 per cent and provides a firm base for a 3-per-cent determination of the Hubble constant, with prospects for improvement to 2 per cent in the future.

doi: 10.1038/nature11878

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材料:CO2分離に最適な吸着熱力学的および動力学的特性を示す多孔性材料

Porous materials with optimal adsorption thermodynamics and kinetics for CO2 separation p.80

The energy costs associated with the separation and purification of industrial commodities, such as gases, fine chemicals and fresh water, currently represent around 15 per cent of global energy production, and the demand for such commodities is projected to triple by 2050 (ref. 1). The challenge of developing effective separation and purification technologies that have much smaller energy footprints is greater for carbon dioxide (CO2) than for other gases; in addition to its involvement in climate change, CO2 is an impurity in natural gas, biogas (natural gas produced from biomass), syngas (CO/H2, the main source of hydrogen in refineries) and many other gas streams. In the context of porous crystalline materials that can exploit both equilibrium and kinetic selectivity, size selectivity and targeted molecular recognition are attractive characteristics for CO2 separation and capture, as exemplified by zeolites 5A and 13X (ref. 2), as well as metal–organic materials (MOMs). Here we report that a crystal engineering or reticular chemistry strategy that controls pore functionality and size in a series of MOMs with coordinately saturated metal centres and periodically arrayed hexafluorosilicate (SiF62−) anions enables a ‘sweet spot’ of kinetics and thermodynamics that offers high volumetric uptake at low CO2 partial pressure (less than 0.15 bar). Most importantly, such MOMs offer an unprecedented CO2 sorption selectivity over N2, H2 and CH4, even in the presence of moisture. These MOMs are therefore relevant to CO2 separation in the context of post-combustion (flue gas, CO2/N2), pre-combustion (shifted synthesis gas stream, CO2/H2) and natural gas upgrading (natural gas clean-up, CO2/CH4).

doi: 10.1038/nature11893

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化学:低温水相メタノール脱水素化による水素と二酸化炭素の生成

Low-temperature aqueous-phase methanol dehydrogenation to hydrogen and carbon dioxide p.85

Hydrogen produced from renewable resources is a promising potential source of clean energy. With the help of low-temperature proton-exchange membrane fuel cells, molecular hydrogen can be converted efficiently to produce electricity. The implementation of sustainable hydrogen production and subsequent hydrogen conversion to energy is called “hydrogen economy”. Unfortunately, its physical properties make the transport and handling of hydrogen gas difficult. To overcome this, methanol can be used as a material for the storage of hydrogen, because it is a liquid at room temperature and contains 12.6 per cent hydrogen. However, the state-of-the-art method for the production of hydrogen from methanol (methanol reforming) is conducted at high temperatures (over 200 degrees Celsius) and high pressures (25–50 bar), which limits its potential applications. Here we describe an efficient low-temperature aqueous-phase methanol dehydrogenation process, which is facilitated by ruthenium complexes. Hydrogen generation by this method proceeds at 65–95 degrees Celsius and ambient pressure with excellent catalyst turnover frequencies (4,700 per hour) and turnover numbers (exceeding 350,000). This would make the delivery of hydrogen on mobile devices—and hence the use of methanol as a practical hydrogen carrier—feasible.

doi: 10.1038/nature11891

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気候科学:スノーボールアースの海洋力学

Dynamics of a Snowball Earth ocean p.90

Geological evidence suggests that marine ice extended to the Equator at least twice during the Neoproterozoic era (about 750 to 635 million years ago), inspiring the Snowball Earth hypothesis that the Earth was globally ice-covered. In a possible Snowball Earth climate, ocean circulation and mixing processes would have set the melting and freezing rates that determine ice thickness, would have influenced the survival of photosynthetic life, and may provide important constraints for the interpretation of geochemical and sedimentological observations. Here we show that in a Snowball Earth, the ocean would have been well mixed and characterized by a dynamic circulation, with vigorous equatorial meridional overturning circulation, zonal equatorial jets, a well developed eddy field, strong coastal upwelling and convective mixing. This is in contrast to the sluggish ocean often expected in a Snowball Earth scenario owing to the insulation of the ocean from atmospheric forcing by the thick ice cover. As a result of vigorous convective mixing, the ocean temperature, salinity and density were either uniform in the vertical direction or weakly stratified in a few locations. Our results are based on a model that couples ice flow and ocean circulation, and is driven by a weak geothermal heat flux under a global ice cover about a kilometre thick. Compared with the modern ocean, the Snowball Earth ocean had far larger vertical mixing rates, and comparable horizontal mixing by ocean eddies. The strong circulation and coastal upwelling resulted in melting rates near continents as much as ten times larger than previously estimated. Although we cannot resolve the debate over the existence of global ice cover, we discuss the implications for the nutrient supply of photosynthetic activity and for banded iron formations. Our insights and constraints on ocean dynamics may help resolve the Snowball Earth controversy when combined with future geochemical and geological observations.

doi: 10.1038/nature11894

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古生物学:ジュラ紀の水陸両生の双翅目昆虫と幼形保有

Amphibious flies and paedomorphism in the Jurassic period p.94

The species of the Strashilidae (strashilids) have been the most perplexing of fossil insects from the Jurassic period of Russia and China. They have been widely considered to be ectoparasites of pterosaurs or feathered dinosaurs, based on the putative presence of piercing and sucking mouthparts and hind tibio-basitarsal pincers purportedly used to fix onto the host’s hairs or feathers. Both the supposed host and parasite occur in the Daohugou beds from the Middle Jurassic epoch of China (approximately 165 million years ago). Here we analyse the morphology of strashilids from the Daohugou beds, and reach markedly different conclusions; namely that strashilids are highly specialized flies (Diptera) bearing large membranous wings, with substantial sexual dimorphism of the hind legs and abdominal extensions. The idea that they belong to an extinct order is unsupported, and the lineage can be placed within the true flies. In terms of major morphological and inferred behavioural features, strashilids resemble the recent (extant) and relict members of the aquatic fly family Nymphomyiidae. Their ontogeny are distinguished by the persistence in adult males of larval abdominal respiratory gills, representing a unique case of paedomorphism among endopterygote insects. Adult strashilids were probably aquatic or amphibious, shedding their wings after emergence and mating in the water.

doi: 10.1038/nature11898

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細胞:NFIBは共有ニッチで上皮–メラノサイト幹細胞の挙動を制御する

NFIB is a governor of epithelial–melanocyte stem cell behaviour in a shared niche p.98

Adult stem cells reside in specialized niches where they receive environmental cues to maintain tissue homeostasis. In mammals, the stem cell niche within hair follicles is home to epithelial hair follicle stem cells and melanocyte stem cells, which sustain cyclical bouts of hair regeneration and pigmentation. To generate pigmented hairs, synchrony is achieved such that upon initiation of a new hair cycle, stem cells of each type activate lineage commitment. Dissecting the inter-stem-cell crosstalk governing this intricate coordination has been difficult, because mutations affecting one lineage often affect the other. Here we identify transcription factor NFIB as an unanticipated coordinator of stem cell behaviour. Hair follicle stem-cell-specific conditional targeting of Nfib in mice uncouples stem cell synchrony. Remarkably, this happens not by perturbing hair cycle and follicle architecture, but rather by promoting melanocyte stem cell proliferation and differentiation. The early production of melanin is restricted to melanocyte stem cells at the niche base. Melanocyte stem cells more distant from the dermal papilla are unscathed, thereby preventing hair greying typical of melanocyte stem cell differentiation mutants. Furthermore, we pinpoint KIT-ligand as a dermal papilla signal promoting melanocyte stem cell differentiation. Additionally, through chromatin-immunoprecipitation with high-throughput-sequencing and transcriptional profiling, we identify endothelin 2 (Edn2) as an NFIB target aberrantly activated in NFIB-deficient hair follicle stem cells. Ectopically induced Edn2 recapitulates NFIB-deficient phenotypes in wild-type mice. Conversely, endothelin receptor antagonists and/or KIT blocking antibodies prevent precocious melanocyte stem cell differentiation in the NFIB-deficient niche. Our findings reveal how melanocyte and hair follicle stem cell behaviours maintain reliance upon cooperative factors within the niche, and how this can be uncoupled in injury, stress and disease states.

doi: 10.1038/nature11847

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分子生物学:創傷治癒の際に起こる、単一転写産物からのマイクロRNA-198とFSTL1の「シーソー型」発現

‘See-saw’ expression of microRNA-198 and FSTL1 from a single transcript in wound healing p.103

Post-transcriptional switches are flexible effectors of dynamic changes in gene expression. Here we report a new post-transcriptional switch that dictates the spatiotemporal and mutually exclusive expression of two alternative gene products from a single transcript. Expression of primate-specific exonic microRNA-198 (miR-198), located in the 3′-untranslated region of follistatin-like 1 (FSTL1) messenger RNA, switches to expression of the linked open reading frame of FSTL1 upon wounding in a human ex vivo organ culture system. We show that binding of a KH-type splicing regulatory protein (KSRP, also known as KHSRP) to the primary transcript determines the fate of the transcript and is essential for the processing of miR-198: transforming growth factor-β signalling switches off miR-198 expression by downregulating KSRP, and promotes FSTL1 protein expression. We also show that FSTL1 expression promotes keratinocyte migration, whereas miR-198 expression has the opposite effect by targeting and inhibiting DIAPH1, PLAU and LAMC2. A clear inverse correlation between the expression pattern of FSTL1 (pro-migratory) and miR-198 (anti-migratory) highlights the importance of this regulatory switch in controlling context-specific gene expression to orchestrate wound re-epithelialization. The deleterious effect of failure of this switch is apparent in non-healing chronic diabetic ulcers, in which expression of miR-198 persists, FSTL1 is absent, and keratinocyte migration, re-epithelialization and wound healing all fail to occur.

doi: 10.1038/nature11890

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老化:マイクロRNA-34aは心臓の老化と機能を調節する

MicroRNA-34a regulates cardiac ageing and function p.107

Ageing is the predominant risk factor for cardiovascular diseases and contributes to a significantly worse outcome in patients with acute myocardial infarction. MicroRNAs (miRNAs) have emerged as crucial regulators of cardiovascular function and some miRNAs have key roles in ageing. We propose that altered expression of miRNAs in the heart during ageing contributes to the age-dependent decline in cardiac function. Here we show that miR-34a is induced in the ageing heart and that in vivo silencing or genetic deletion of miR-34a reduces age-associated cardiomyocyte cell death. Moreover, miR-34a inhibition reduces cell death and fibrosis following acute myocardial infarction and improves recovery of myocardial function. Mechanistically, we identified PNUTS (also known as PPP1R10) as a novel direct miR-34a target, which reduces telomere shortening, DNA damage responses and cardiomyocyte apoptosis, and improves functional recovery after acute myocardial infarction. Together, these results identify age-induced expression of miR-34a and inhibition of its target PNUTS as a key mechanism that regulates cardiac contractile function during ageing and after acute myocardial infarction, by inducing DNA damage responses and telomere attrition.

doi: 10.1038/nature11919

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分子生物学:不適合コドンの使用は時計タンパク質FRQの発現、構造および機能に影響を与える

Non-optimal codon usage affects expression, structure and function of clock protein FRQ p.111

Codon-usage bias has been observed in almost all genomes and is thought to result from selection for efficient and accurate translation of highly expressed genes. Codon usage is also implicated in the control of transcription, splicing and RNA structure. Many genes exhibit little codon-usage bias, which is thought to reflect a lack of selection for messenger RNA translation. Alternatively, however, non-optimal codon usage may be of biological importance. The rhythmic expression and the proper function of the Neurospora FREQUENCY (FRQ) protein are essential for circadian clock function. Here we show that, unlike most genes in Neurospora, frq exhibits non-optimal codon usage across its entire open reading frame. Optimization of frq codon usage abolishes both overt and molecular circadian rhythms. Codon optimization not only increases FRQ levels but, unexpectedly, also results in conformational changes in FRQ protein, altered FRQ phosphorylation profile and stability, and impaired functions in the circadian feedback loops. These results indicate that non-optimal codon usage of frq is essential for its circadian clock function. Our study provides an example of how non-optimal codon usage functions to regulate protein expression and to achieve optimal protein structure and function.

doi: 10.1038/nature11833

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分子生物学:不適合コドンの使用は概日時計の条件制限性を成立させる機構となっている

Non-optimal codon usage is a mechanism to achieve circadian clock conditionality p.116

Circadian rhythms are oscillations in biological processes that function as a key adaptation to the daily rhythms of most environments. In the model cyanobacterial circadian clock system, the core oscillator proteins are encoded by the gene cluster kaiABC. Genes with high expression and functional importance, such as the kai genes, are usually encoded by optimal codons, yet the codon-usage bias of the kaiBC genes is not optimized for translational efficiency. We discovered a relationship between codon usage and a general property of circadian rhythms called conditionality; namely, that endogenous rhythmicity is robustly expressed under some environmental conditions but not others. Despite the generality of circadian conditionality, however, its molecular basis is unknown for any system. Here we show that in the cyanobacterium Synechococcus elongate, non-optimal codon usage was selected as a post-transcriptional mechanism to switch between circadian and non-circadian regulation of gene expression as an adaptive response to environmental conditions. When the kaiBC sequence was experimentally optimized to enhance expression of the KaiB and KaiC proteins, intrinsic rhythmicity was enhanced at cool temperatures that are experienced by this organism in its natural habitat. However, fitness at those temperatures was highest in cells in which the endogenous rhythms were suppressed at cool temperatures as compared with cells exhibiting high-amplitude rhythmicity. These results indicate natural selection against circadian systems in cyanobacteria that are intrinsically robust at cool temperatures. Modulation of circadian amplitude is therefore crucial to its adaptive significance. Moreover, these results show the direct effects of codon usage on a complex phenotype and organismal fitness. Our work also challenges the long-standing view of directional selection towards optimal codons, and provides a key example of natural selection against optimal codons to achieve adaptive responses to environmental changes.

doi: 10.1038/nature11942

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分子生物学:CPEB1は選択的3′-UTR形成を翻訳調節と協調させる

CPEB1 coordinates alternative 3′-UTR formation with translational regulation p.121

More than half of mammalian genes generate multiple messenger RNA isoforms that differ in their 3′ untranslated regions (3′ UTRs) and therefore in regulatory sequences, often associated with cell proliferation and cancer; however, the mechanisms coordinating alternative 3′-UTR processing for specific mRNA populations remain poorly defined. Here we report that the cytoplasmic polyadenylation element binding protein 1 (CPEB1), an RNA-binding protein that regulates mRNA translation, also controls alternative 3′-UTR processing. CPEB1 shuttles to the nucleus, where it co-localizes with splicing factors and mediates shortening of hundreds of mRNA 3′ UTRs, thereby modulating their translation efficiency in the cytoplasm. CPEB1-mediated 3′-UTR shortening correlates with cell proliferation and tumorigenesis. CPEB1 binding to pre-mRNAs not only directs the use of alternative polyadenylation sites, but also changes alternative splicing by preventing U2AF65 recruitment. Our results reveal a novel function of CPEB1 in mediating alternative 3′-UTR processing, which is coordinated with regulation of mRNA translation, through its dual nuclear and cytoplasmic functions.

doi: 10.1038/nature11901

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