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Origins of Atlantic decadal swings p.284

Temperature variability in the North Atlantic Ocean is the result of many competing physical processes, but the relative roles of these processes is a source of contention. Here, scientists present two perspectives on the debate.

Gabriel A. Vecchi, Thomas L. Delworth & Ben Booth

doi: 10.1038/nature23538

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A bitter–sweet symphony p.285

Information about taste sensations, such as bitter or sweet, is relayed from the mouse tongue to the brain through taste-specific pathways. It emerges that semaphorin proteins guide the wiring of these pathways. See Letter p.330

Jiefu Li & Liqun Luo

doi: 10.1038/nature23537

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Human metastases under scrutiny p.287

Sequences of the DNA and RNA of 500 human cancers that have spread from their primary site in the body take us a step closer to the convergence of basic science and patient benefit. See Article p.297

G. Steven Bova

doi: 10.1038/nature23535

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A turbulent stellar atmosphere in full view p.288

The dynamic motion of gas in the outer atmosphere of a red supergiant star has been mapped, providing clues to the mysterious mechanism that causes massive stars to lose mass through stellar winds. See Letter p.310

Gail H. Schaefer

doi: 10.1038/548288a

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Healthy skin rejects cancer p.289

Live imaging shows that healthy skin cells surround and expel neighbours that have cancer-promoting mutations, revealing that tissues can recognize and eliminate mutant cells to prevent tumour initiation. See Letter p.334

Joseph Burclaff & Jason C. Mills

doi: 10.1038/nature23534

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Articles

New gliding mammaliaforms from the Jurassic p.291

Maiopatagium, a haramiyid from the Jurassic Tiaojishan Formation (around 160 million years ago) of China was specialised for gliding with a patagium (wing membrane) and a fused wishbone, reminiscent of that of birds.

Qing-Jin Meng, David M. Grossnickle, Di Liu, Yu-Guang Zhang, April I. Neander, Qiang Ji & Zhe-Xi Luo

doi: 10.1038/nature23476

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Integrative clinical genomics of metastatic cancer p.297

Clinical exome and transcriptome sequencing of 500 adult patients with metastatic solid tumours of diverse lineage and biopsy site, as part of the Michigan Oncology Sequencing (MI-ONCOSEQ) Program.

Dan R. Robinson, Yi-Mi Wu, Robert J. Lonigro, Pankaj Vats, Erin Cobain, Jessica Everett, Xuhong Cao, Erica Rabban, Chandan Kumar-Sinha, Victoria Raymond + et al.

doi: 10.1038/nature23306

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Letters

Ram-pressure feeding of supermassive black holes p.304

The majority of ‘jellyfish’ galaxies, characterized by long ‘tentacles’ of gas, also have active nuclei, indicating that gas is being fed to the central supermassive black hole by ram pressure.

Bianca M. Poggianti, Yara L. Jaffé, Alessia Moretti, Marco Gullieuszik, Mario Radovich, Stephanie Tonnesen, Jacopo Fritz, Daniela Bettoni, Benedetta Vulcani, Giovanni Fasano + et al.

doi: 10.1038/nature23462

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Vigorous atmospheric motion in the red supergiant star Antares p.310

Mapping the velocity of the gas at the surface and in the atmosphere of the nearby red supergiant star Antares reveals vigorous motion of several huge gas clumps in an extended atmosphere, which cannot be fully explained by convection.

K. Ohnaka, G. Weigelt & K.-H. Hofmann

doi: 10.1038/nature23445

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An early modern human presence in Sumatra 73,000–63,000 years ago p.322

Morphological analysis of teeth found at Lida Ajer shows that these belong to Homo sapiens, indicating that modern humans were in Sumatra between 73,000 and 63,000 years ago.

K. E. Westaway, J. Louys, R. Due Awe, M. J. Morwood, G. J. Price, J.-x. Zhao, M. Aubert, R. Joannes-Boyau, T. M. Smith, M. M. Skinner + et al.

doi: 10.1038/nature23452

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Rewiring the taste system p.330

Taste-receptor cells use distinct semaphorins to guide wiring of the peripheral taste system; targeted ectopic expression of SEMA3A or SEMA7A leads to bitter neurons responding to sweet tastes or sweet neurons responding to bitter tastes.

Hojoon Lee, Lindsey J. Macpherson, Camilo A. Parada, Charles S. Zuker & Nicholas J. P. Ryba

doi: 10.1038/nature23299

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Correction of aberrant growth preserves tissue homeostasis p.334

Intravital imaging reveals unanticipated plasticity of adult skin epithelium in mice when faced with mutational or non-mutational insults, and elucidates the dynamic cellular behaviours used for its return to a homeostatic state.

Samara Brown, Cristiana M. Pineda, Tianchi Xin, Jonathan Boucher, Kathleen C. Suozzi, Sangbum Park, Catherine Matte-Martone, David G. Gonzalez, Julie Rytlewski, Slobodan Beronja + et al.

doi: 10.1038/nature23304

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m6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways p.338

N6-methyladenosine (m6A) is the most common and abundant messenger RNA modification, modulated by ‘writers’, ‘erasers’ and ‘readers’ of this mark. In vitro data have shown that m6A influences all fundamental aspects of mRNA metabolism, mainly mRNA stability, to determine stem cell fates. However, its in vivo physiological function in mammals and adult mammalian cells is still unknown. Here we show that the deletion of m6A ‘writer’ protein METTL3 in mouse T cells disrupts T cell homeostasis and differentiation. In a lymphopaenic mouse adoptive transfer model, naive Mettl3-deficient T cells failed to undergo homeostatic expansion and remained in the naive state for up to 12 weeks, thereby preventing colitis. Consistent with these observations, the mRNAs of SOCS family genes encoding the STAT signalling inhibitory proteins SOCS1, SOCS3 and CISH were marked by m6A, exhibited slower mRNA decay and showed increased mRNAs and levels of protein expression in Mettl3-deficient naive T cells. This increased SOCS family activity consequently inhibited IL-7-mediated STAT5 activation and T cell homeostatic proliferation and differentiation. We also found that m6A has important roles for inducible degradation of Socs mRNAs in response to IL-7 signalling in order to reprogram naive T cells for proliferation and differentiation. Our study elucidates for the first time, to our knowledge, the in vivo biological role of m6A modification in T-cell-mediated pathogenesis and reveals a novel mechanism of T cell homeostasis and signal-dependent induction of mRNA degradation.

Hua-Bing Li, Jiyu Tong, Shu Zhu, Pedro J. Batista, Erin E. Duffy, Jun Zhao, Will Bailis, Guangchao Cao, Lina Kroehling, Yuanyuan Chen + et al.

doi: 10.1038/nature23450

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Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood p.343

Long noncoding RNAs are investigated using a CRISPR–Cas9 activation screen and shown to confer BRAF inhibitor resistance on melanoma cells through various local mechanisms.

Julia Joung, Jesse M. Engreitz, Silvana Konermann, Omar O. Abudayyeh, Vanessa K. Verdine, Francois Aguet, Jonathan S. Gootenberg, Neville E. Sanjana, Jason B. Wright, Charles P. Fulco + et al.

doi: 10.1038/nature23451

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mRNA 3′ uridylation and poly(A) tail length sculpt the mammalian maternal transcriptome p.347

A fundamental principle in biology is that the program for early development is established during oogenesis in the form of the maternal transcriptome. How the maternal transcriptome acquires the appropriate content and dosage of transcripts is not fully understood. Here we show that 3′ terminal uridylation of mRNA mediated by TUT4 and TUT7 sculpts the mouse maternal transcriptome by eliminating transcripts during oocyte growth. Uridylation mediated by TUT4 and TUT7 is essential for both oocyte maturation and fertility. In comparison to somatic cells, the oocyte transcriptome has a shorter poly(A) tail and a higher relative proportion of terminal oligo-uridylation. Deletion of TUT4 and TUT7 leads to the accumulation of a cohort of transcripts with a high frequency of very short poly(A) tails, and a loss of 3′ oligo-uridylation. By contrast, deficiency of TUT4 and TUT7 does not alter gene expression in a variety of somatic cells. In summary, we show that poly(A) tail length and 3′ terminal uridylation have essential and specific functions in shaping a functional maternal transcriptome.

Marcos Morgan, Christian Much, Monica DiGiacomo, Chiara Azzi, Ivayla Ivanova, Dimitrios M. Vitsios, Jelena Pistolic, Paul Collier, Pedro N. Moreira, Vladimir Benes + et al.

doi: 10.1038/nature23318

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Cryo-EM structure of the protein-conducting ERAD channel Hrd1 in complex with Hrd3 p.352

The structure of yeast Hrd1 in complex with Hrd3 shows that Hrd1 forms an aqueous cavity with a lateral seal within the endoplasmic reticulum membrane, shedding light on how misfolded proteins are transported out of the endoplasmic reticulum.

Stefan Schoebel, Wei Mi, Alexander Stein, Sergey Ovchinnikov, Ryan Pavlovicz, Frank DiMaio, David Baker, Melissa G. Chambers, Huayou Su, Dongsheng Li + et al.

doi: 10.1038/nature23314

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Structural insights into ligand recognition by the lysophosphatidic acid receptor LPA6 p.356

Determination of the crystal structure of the zebrafish LPA6 receptor shows that the lipid ligand binds to an unusual ligand-binding pocket in the receptor that is laterally accessible through the membrane.

Reiya Taniguchi, Asuka Inoue, Misa Sayama, Akiharu Uwamizu, Keitaro Yamashita, Kunio Hirata, Masahito Yoshida, Yoshiki Tanaka, Hideaki E. Kato, Yoshiko Nakada-Nakura + et al.

doi: 10.1038/nature23448

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