• 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
    •  & Jin Billy Li
  • Article |

    Neuromedin receptor NMUR1 is specifically expressed by a subpopulation of type 2 innate lymphoid cells and promotes the inflammatory response of these cells in response to allergens, indicating the importance of neuro-immune crosstalk in allergic responses.

    • Antonia Wallrapp
    • , Samantha J. Riesenfeld
    •  & Vijay K. Kuchroo
  • Letter |

    Under stress, such as heat shock, the N6-methyladenosine (m6A) modification is shown to accumulate primarily in the 5′ untranslated region of induced mRNAs owing to the translocation of an m6A interacting protein, YTHDF2, into the nucleus, resulting in increased cap-independent translation of these mRNAs, indicating one possible mechanism by which stress-responsive genes can be preferentially expressed.

    • Jun Zhou
    • , Ji Wan
    •  & Shu-Bing Qian
  • Letter |

    The single-stranded nature of RNAs synthesized in the cell gives them great scope to form different structures, but current methods to measure RNA structure in vivo are limited; now, a new methodology allows researchers to examine all four nucleotides in mouse embryonic stem cells.

    • Robert C. Spitale
    • , Ryan A. Flynn
    •  & Howard Y. Chang
  • Letter |

    It has been known for some time that limbs share at least some of their molecular patterning mechanism with external genitalia; here, this connection is examined in a variety of species, revealing that once-shared developmental trajectories could help to explain the observed patterning similarities.

    • Patrick Tschopp
    • , Emma Sherratt
    •  & Clifford J. Tabin
  • Letter |

    The authors perform saturation mutagenesis of genomic regions in their native endogenous chromosomal context by using CRISPR/Cas9 RNA-guided cleavage and multiplex homology-directed repair; its utility is demonstrated by measuring the effects of hundreds to thousands of genomic edits to BRCA1 and DBR1 on splicing and cellular fitness, respectively.

    • Gregory M. Findlay
    • , Evan A. Boyle
    •  & Jay Shendure
  • Letter
    | Open Access

    Uniform processing and detailed annotation of human, worm and fly RNA-sequencing data reveal ancient, conserved features of the transcriptome, shared co-expression modules (many enriched in developmental genes), matched expression patterns across development and similar extent of non-canonical, non-coding transcription; furthermore, the data are used to create a single, universal model to predict gene-expression levels for all three organisms from chromatin features at the promoter.

    • Mark B. Gerstein
    • , Joel Rozowsky
    •  & Robert Waterston
  • Article |

    Using the FANTOM5 CAGE expression atlas, the authors show that bidirectional capped RNAs are a signature feature of active enhancers and identify over 40,000 enhancer candidates from over 800 human cell and tissue samples across the whole human body.

    • Robin Andersson
    • , Claudia Gebhard
    •  & Albin Sandelin
  • Article |

    A study from the FANTOM consortium using single-molecule cDNA sequencing of transcription start sites and their usage in human and mouse primary cells, cell lines and tissues reveals insights into the specificity and diversity of transcription patterns across different mammalian cell types.

    • Alistair R. R. Forrest
    • , Hideya Kawaji
    •  & Yoshihide Hayashizaki
  • Article
    | Open Access

    A large-scale transcriptome analysis in Drosophila melanogaster, across tissues, cell types and conditions, provides insights into global patterns and diversity of transcription initiation, splicing, polyadenylation and non-coding RNA expression.

    • James B. Brown
    • , Nathan Boley
    •  & Susan E. Celniker
  • Letter |

    The transcription start sites used during the maternal to zygotic transition in zebrafish are mapped, revealing that the transition is characterized by a switch between two different sequence signs to guide transcription initiation, which often co-exist in core promoters.

    • Vanja Haberle
    • , Nan Li
    •  & Boris Lenhard
  • Letter |

    An RNA secondary structure (RSS) map of coding and noncoding RNA from a human family (two parents and their child) is produced; this reveals that approximately 15% of all transcribed single nucleotide variants (SNVs) alter local RNA structure, and these SNVs are depleted in certain locations, suggesting that particular RNA structures are important at those sites.

    • Yue Wan
    • , Kun Qu
    •  & Howard Y. Chang
  • Article |

    Naturally occurring genetic variation between inbred mouse strains is used as a mutagenesis strategy to investigate mechanisms responsible for the selection and function of cis-regulatory elements in macrophages; lineage-determining transcription factors are proposed to select enhancer-like regions in the genome in a collaborative fashion and facilitate the binding of signal-dependent factors.

    • S. Heinz
    • , C. E. Romanoski
    •  & C. K. Glass
  • Article |

    Sequencing and deep analysis of mRNA and miRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project reveal widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent, and the analyses point to putative causal variants for dozens of disease-associated loci.

    • Tuuli Lappalainen
    • , Michael Sammeth
    •  & Emmanouil T. Dermitzakis
  • Letter |

    This study identifies MBNL proteins as negative regulators of alternative splicing events that are differentially regulated between ES cells and other cell types; several lines of evidence show that these proteins repress an ES cell alternative splicing program and the reprogramming of somatic cells to induced pluripotent stem cells.

    • Hong Han
    • , Manuel Irimia
    •  & Benjamin J. Blencowe
  • Letter |

    Single-cell RNA sequencing is used to investigate the transcriptional response of 18 mouse bone-marrow-derived dendritic cells after lipopolysaccharide stimulation; many highly expressed genes, such as key immune genes and cytokines, show bimodal variation in both transcript abundance and splicing patterns. This variation reflects differences in both cell state and usage of an interferon-driven pathway involving Stat2 and Irf7.

    • Alex K. Shalek
    • , Rahul Satija
    •  & Aviv Regev
  • Letter |

    Variation among RNA transcript isoforms can be generated from alternative start and polyadenylation sites, and results in RNAs and proteins with different properties being generated from the same genomic sequence; here a new method termed transcript isoform sequencing is described in yeast, and the method allows a fuller exploration of transcriptome diversity across the compact yeast genome.

    • Vicent Pelechano
    • , Wu Wei
    •  & Lars M. Steinmetz
  • Article |

    Laser microdissection and microarrays are used to assess 900 precise subdivisions of the brains from three healthy men with 60,000 gene expression probes; the resulting atlas allows comparisons between humans and other animals, and will facilitate studies of human neurological and psychiatric diseases.

    • Michael J. Hawrylycz
    • , Ed S. Lein
    •  & Allan R. Jones
  • Letter |

    As it develops from a single-celled zygote to a mature plant embryo, the thale cress Arabidopsis thaliana passes through a stage during which phylogenetically very ancient genes are preferentially expressed, showing that animals and plants have independently acquired the developmental hourglass as a similar way of managing gene expression as they pass through embryogenesis, even though their morphological development is very different.

    • Marcel Quint
    • , Hajk-Georg Drost
    •  & Ivo Grosse
  • Article
    | Open Access

    A description is given of the ENCODE effort to provide a complete catalogue of primary and processed RNAs found either in specific subcellular compartments or throughout the cell, revealing that three-quarters of the human genome can be transcribed, and providing a wealth of information on the range and levels of expression, localization, processing fates and modifications of known and previously unannotated RNAs.

    • Sarah Djebali
    • , Carrie A. Davis
    •  & Thomas R. Gingeras
  • Letter |

    MicroRNA in worms is shown to target non-coding primary microRNA transcripts through interaction with the Argonaute protein, promoting the production of further microRNA and thus generating a positive-feedback loop.

    • Dimitrios G. Zisoulis
    • , Zoya S. Kai
    •  & Amy E. Pasquinelli
  • Article |

    N6-methyladenosine (m6A) is the most prevalent internal modification in messenger RNA; here the human and mouse m6A modification landscape is presented in a transcriptome-wide manner, providing insights into this epigenetic modification.

    • Dan Dominissini
    • , Sharon Moshitch-Moshkovitz
    •  & Gideon Rechavi
  • Letter |

    Secondary structures, or pairing of complementary sequences within RNA, can regulate the binding of proteins that affect transcript stability, splicing, localization, and translation; a computational approach has now been used to discover secondary structures that affect global RNA stability through the binding of specific RNA binding proteins.

    • Hani Goodarzi
    • , Hamed S. Najafabadi
    •  & Saeed Tavazoie
  • Letter |

    The nuclear receptors REV-ERB-α and REV-ERB-β are indispensible for the coordination of circadian rhythm and metabolism; mice without these nuclear receptors show disrupted circadian expression of core circadian clock and lipid homeostatic gene networks.

    • Han Cho
    • , Xuan Zhao
    •  & Ronald M. Evans
  • Article |

    As part of the modENCODE initiative, which aims to characterize functional DNA elements in D. melanogaster and C. elegans, this study uses RNA-Seq, tiling microarrays and cDNA sequencing to explore the transcriptome in 30 distinct developmental stages of the fruitfly. Among the results are scores of new genes, coding and non-coding transcripts, as well as splicing and editing events.

    • Brenton R. Graveley
    • , Angela N. Brooks
    •  & Susan E. Celniker
  • Letter |

    Here, sequencing has been used to characterize the mRNA fraction of the transcriptome in Caucasian individuals, to provide a fine-scale view of transcriptomes and to identify genetic variants that affect alternative splicing. Measuring allele-specific expression identified rare expression quantitative trait loci (eQTLs) and allelic differences in transcript structure, revealing new properties of genetic effects on the transcriptome.

    • Stephen B. Montgomery
    • , Micha Sammeth
    •  & Emmanouil T. Dermitzakis
  • Article |

    The transcriptome of Helicobacter pylori, an important human pathogen involved in gastric ulcers and cancer, is presented. The approach establishes a model for mapping and annotating the primary transcriptomes of many living species.

    • Cynthia M. Sharma
    • , Steve Hoffmann
    •  & Jörg Vogel