Volume 550 Issue 7675, 12 October 2017

Volume 550 Issue 7675

The GTEx (Genotype-Tissue Expression) Consortium has established a reference catalogue and associated tissue biobank for gene-expression levels across individuals for diverse tissues of the human body, with a broad sampling of normal, non-diseased human tissues from postmortem donors. In an Article, the consortium presents the deepest survey of gene expression across multiple tissues and individuals to date, encompassing 7,051 samples from 449 donors across 44 human tissues. They characterize the relationship between genetic variation and gene expression across tissues and individuals, and find that most genes are regulated by genetic variation near to the affected gene. In accompanying Letters, Alexis Battle, Stephen Montgomery and their colleagues examine the impact of rare genetic variation on gene expression across human tissues. Daniel MacArthur and his team systematically survey the landscape of X chromosome inactivation in human tissues. And Jin Billy Li and his colleagues provide a comprehensive cross-species analysis of adenosine-to-inosine RNA editing in mammals. In an accompanying News & Views, Michelle Ward and Yoav Gilad put the latest results in context and discuss how these findings are helping to crack the regulatory code of the human genome. Cover image: Concept design: Christine A. Dahl. Graphics: Norm Cyr, Science Illustrator, Department of Pathology, Stanford Medicine

This Week

News In Focus

Comment

Careers

Specials

    Technology Feature

  • Outlook

  • Outlook |

    The increasing acidity of our seas is a threat to marine life that for many species may be impossible to overcome.

    • Sarah DeWeerdt

    Nature Outlook:

  • Outlook |

    In the scientific community, the big question is not whether action on climate change is required, but what form it should take — and the part that scientists should play. Three Nobel laureates and three early-career researchers gave their thoughts to Nature on the current state of climate action worldwide and the place of science in society.

    • Peter Agre
    • , Mario Molina
    •  & Steven Chu

    Nature Outlook:

  • Outline

Research

    News & Views

  • News & Views |

    Pariahs are fundamental building blocks in a branch of mathematics called group theory, but seem to be unconnected from both physics and other areas of mathematics. Such a connection has now been identified.

    • Terry Gannon
  • News & Views |

    Cancer cells can develop an 'addiction' to the drugs they are treated with, so that they need the drugs to survive. Analysis of the underlying mechanism reveals a potential clinical strategy for harnessing this phenomenon. See Letter p.270

    • Rebecca J. Lee
    •  & Richard Marais
  • News & Views |

    Although liquid metals are effective fluids for heat transfer, pumping them at high temperatures is limited by their corrosiveness to solid metals. A clever pump design addresses this challenge using only ceramics. See Article p.199

    • Konstantina Lambrinou
  • News & Views |

    Observations of the distant dwarf planet Haumea constrain its size, shape and density, and reveal an encircling planetary ring. The discovery suggests that rings are not as rare in the Solar System as previously thought. See Letter p.219

    • Amanda A. Sickafoose
  • Articles

  • Article |

    By using ceramics for the mechanical and sealing components of a mechanical pump, liquid metal can be circulated continuously at temperatures at least as high as 1,673 kelvin.

    • C. Amy
    • , D. Budenstein
    • , M. Bagepalli
    • , D. England
    • , F. DeAngelis
    • , G. Wilk
    • , C. Jarrett
    • , C. Kelsall
    • , J. Hirschey
    • , H. Wen
    • , A. Chavan
    • , B. Gilleland
    • , C. Yuan
    • , W. C. Chueh
    • , K. H. Sandhage
    • , Y. Kawajiri
    •  & A. Henry
  • Article |

    In Escherichia coli, the control of RNA polymerase backtracking by transcription elongation factors impairs DNA break repair by affecting RecBCD resection and consequently RecA loading at sites far removed from the original DNA break.

    • Priya Sivaramakrishnan
    • , Leonardo A. Sepúlveda
    • , Jennifer A. Halliday
    • , Jingjing Liu
    • , María Angélica Bravo Núñez
    • , Ido Golding
    • , Susan M. Rosenberg
    •  & Christophe Herman
  • Letters

  • Letter |

    Observations of a stellar occultation of Haumea, one of the four known trans-Neptunian dwarf planets, constrain its size, shape and density, and reveal a ring coplanar with Haumea’s largest moon.

    • J. L. Ortiz
    • , P. Santos-Sanz
    • , B. Sicardy
    • , G. Benedetti-Rossi
    • , D. Bérard
    • , N. Morales
    • , R. Duffard
    • , F. Braga-Ribas
    • , U. Hopp
    • , C. Ries
    • , V. Nascimbeni
    • , F. Marzari
    • , V. Granata
    • , A. Pál
    • , C. Kiss
    • , T. Pribulla
    • , R. Komžík
    • , K. Hornoch
    • , P. Pravec
    • , P. Bacci
    • , M. Maestripieri
    • , L. Nerli
    • , L. Mazzei
    • , M. Bachini
    • , F. Martinelli
    • , G. Succi
    • , F. Ciabattari
    • , H. Mikuz
    • , A. Carbognani
    • , B. Gaehrken
    • , S. Mottola
    • , S. Hellmich
    • , F. L. Rommel
    • , E. Fernández-Valenzuela
    • , A. Campo Bagatin
    • , S. Cikota
    • , A. Cikota
    • , J. Lecacheux
    • , R. Vieira-Martins
    • , J. I. B. Camargo
    • , M. Assafin
    • , F. Colas
    • , R. Behrend
    • , J. Desmars
    • , E. Meza
    • , A. Alvarez-Candal
    • , W. Beisker
    • , A. R. Gomes-Junior
    • , B. E. Morgado
    • , F. Roques
    • , F. Vachier
    • , J. Berthier
    • , T. G. Mueller
    • , J. M. Madiedo
    • , O. Unsalan
    • , E. Sonbas
    • , N. Karaman
    • , O. Erece
    • , D. T. Koseoglu
    • , T. Ozisik
    • , S. Kalkan
    • , Y. Guney
    • , M. S. Niaei
    • , O. Satir
    • , C. Yesilyaprak
    • , C. Puskullu
    • , A. Kabas
    • , O. Demircan
    • , J. Alikakos
    • , V. Charmandaris
    • , G. Leto
    • , J. Ohlert
    • , J. M. Christille
    • , R. Szakáts
    • , A. Takácsné Farkas
    • , E. Varga-Verebélyi
    • , G. Marton
    • , A. Marciniak
    • , P. Bartczak
    • , T. Santana-Ros
    • , M. Butkiewicz-Bąk
    • , G. Dudziński
    • , V. Alí-Lagoa
    • , K. Gazeas
    • , L. Tzouganatos
    • , N. Paschalis
    • , V. Tsamis
    • , A. Sánchez-Lavega
    • , S. Pérez-Hoyos
    • , R. Hueso
    • , J. C. Guirado
    • , V. Peris
    •  & R. Iglesias-Marzoa
  • Letter |

    Light-field-driven control of electrons in a conductor is demonstrated by inducing a current by laser pulses in graphene that is sensitive to the carrier-envelope phase.

    • Takuya Higuchi
    • , Christian Heide
    • , Konrad Ullmann
    • , Heiko B. Weber
    •  & Peter Hommelhoff
  • Letter |

    By exploiting geometric constraints and interfacial forces instead of chemistry, colloidal clusters can be controllably coalesced into particles with uniformly distributed surface patches.

    • Zhe Gong
    • , Theodore Hueckel
    • , Gi-Ra Yi
    •  & Stefano Sacanna
  • Letter | | open

    The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

    • Xin Li
    • , Yungil Kim
    • , Emily K. Tsang
    • , Joe R. Davis
    • , Farhan N. Damani
    • , Colby Chiang
    • , Gaelen T. Hess
    • , Zachary Zappala
    • , Benjamin J. Strober
    • , Alexandra J. Scott
    • , Amy Li
    • , Andrea Ganna
    • , Michael C. Bassik
    • , Jason D. Merker
    • , GTEx Consortium
    • , Ira M. Hall
    • , Alexis Battle
    •  & Stephen B. Montgomery
  • Letter | | open

    Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.

    • Taru Tukiainen
    • , Alexandra-Chloé Villani
    • , Angela Yen
    • , Manuel A. Rivas
    • , Jamie L. Marshall
    • , Rahul Satija
    • , Matt Aguirre
    • , Laura Gauthier
    • , Mark Fleharty
    • , Andrew Kirby
    • , Beryl B. Cummings
    • , Stephane E. Castel
    • , Konrad J. Karczewski
    • , François Aguet
    • , Andrea Byrnes
    • , GTEx Consortium
    • , Tuuli Lappalainen
    • , Aviv Regev
    • , Kristin G. Ardlie
    • , Nir Hacohen
    •  & Daniel G. MacArthur
  • Letter |

    Using the GTEx data and others, a comprehensive analysis of adenosine-to-inosine RNA editing in mammals is presented; targets of the various ADAR enzymes are identified, as are several potential regulators of editing, such as AIMP2.

    • Meng How Tan
    • , Qin Li
    • , Raghuvaran Shanmugam
    • , Robert Piskol
    • , Jennefer Kohler
    • , Amy N. Young
    • , Kaiwen Ivy Liu
    • , Rui Zhang
    • , Gokul Ramaswami
    • , Kentaro Ariyoshi
    • , Ankita Gupte
    • , Liam P. Keegan
    • , Cyril X. George
    • , Avinash Ramu
    • , Ni Huang
    • , Elizabeth A. Pollina
    • , Dena S. Leeman
    • , Alessandra Rustighi
    • , Y. P. Sharon Goh
    • , GTEx Consortium
    • , Ajay Chawla
    • , Giannino Del Sal
    • , Gary Peltz
    • , Anne Brunet
    • , Donald F. Conrad
    • , Charles E. Samuel
    • , Mary A. O’Connell
    • , Carl R. Walkley
    • , Kazuko Nishikura
    •  & Jin Billy Li
  • Letter |

    GDNF receptor alpha-like is a brainstem-restricted receptor for growth and differentiation factor 15, regulating appetite and body weight in non-homeostatic conditions by activating the emergency circuit response to disease and toxin stresses.

    • Jer-Yuan Hsu
    • , Suzanne Crawley
    • , Michael Chen
    • , Dina A. Ayupova
    • , Darrin A. Lindhout
    • , Jared Higbee
    • , Alan Kutach
    • , William Joo
    • , Zhengyu Gao
    • , Diana Fu
    • , Carmen To
    • , Kalyani Mondal
    • , Betty Li
    • , Avantika Kekatpure
    • , Marilyn Wang
    • , Teresa Laird
    • , Geoffrey Horner
    • , Jackie Chan
    • , Michele McEntee
    • , Manuel Lopez
    • , Damodharan Lakshminarasimhan
    • , Andre White
    • , Sheng-Ping Wang
    • , Jun Yao
    • , Junming Yie
    • , Hugo Matern
    • , Mark Solloway
    • , Raj Haldankar
    • , Thomas Parsons
    • , Jie Tang
    • , Wenyan D. Shen
    • , Yu Alice Chen
    • , Hui Tian
    •  & Bernard B. Allan
  • Letter |

    Deletion of the Hippo pathway component Salvador in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function.

    • John P. Leach
    • , Todd Heallen
    • , Min Zhang
    • , Mahdis Rahmani
    • , Yuka Morikawa
    • , Matthew C. Hill
    • , Ana Segura
    • , James T. Willerson
    •  & James F. Martin
  • Letter |

    In budding yeast, glucose withdrawal, via the Rag GTPases, leads to TORC1 inhibition through its re-organization into a giant, vacuole-associated helix named a TOROID (TORC1 organized in inhibited domain).

    • Manoël Prouteau
    • , Ambroise Desfosses
    • , Christian Sieben
    • , Clélia Bourgoint
    • , Nour Lydia Mozaffari
    • , Davide Demurtas
    • , Alok K. Mitra
    • , Paul Guichard
    • , Suliana Manley
    •  & Robbie Loewith
  • Letter |

    The identification of an ERK2–JUNB–FRA1 signalling pathway that drives addiction to therapeutic drugs in cancer cells, and an ERK2-dependent phenotype switch that precedes cell death after drug withdrawal, may help to guide therapies that exploit the addiction phenotype.

    • Xiangjun Kong
    • , Thomas Kuilman
    • , Aida Shahrabi
    • , Julia Boshuizen
    • , Kristel Kemper
    • , Ji-Ying Song
    • , Hans W. M. Niessen
    • , Elisa A. Rozeman
    • , Marnix H. Geukes Foppen
    • , Christian U. Blank
    •  & Daniel S. Peeper
  • Letter |

    The class 2 type VI RNA-guided RNA-targeting CRISPR–Cas effector Cas13 can be engineered for RNA knockdown and binding, expanding the CRISPR toolset with a flexible platform for studying RNA in mammalian cells and therapeutic development.

    • Omar O. Abudayyeh
    • , Jonathan S. Gootenberg
    • , Patrick Essletzbichler
    • , Shuo Han
    • , Julia Joung
    • , Joseph J. Belanto
    • , Vanessa Verdine
    • , David B. T. Cox
    • , Max J. Kellner
    • , Aviv Regev
    • , Eric S. Lander
    • , Daniel F. Voytas
    • , Alice Y. Ting
    •  & Feng Zhang

Corrections

Newsletter Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing