Landscape of transcription in human cells

Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.     

The intense starburst HDF 850.1 in a galaxy overdensity at z ≈ 5.2 in the Hubble Deep Field

The Hubble Deep Field provides one of the deepest multiwavelength views of the distant Universe and has led to the detection of thousands of galaxies seen throughout cosmic time. An early map of the Hubble Deep Field at a wavelength of 850?micrometres, which is sensitive to dust emission powered by star formation, revealed the brightest source in the field, dubbed HDF?850.1 (ref. 2). For more than a decade, and despite significant efforts, no counterpart was found at shorter wavelengths, and it was not possible to determine its redshift, size or mass. Here we report a redshift of z = 5.183 for HDF?850.1, from a millimetre-wave molecular line scan. This places HDF?850.1 in a galaxy overdensity at z?≈?5.2, corresponding to a cosmic age of only 1.1?billion years after the Big Bang. This redshift is significantly higher than earlier estimates and higher than those of most of the hundreds of submillimetre-bright galaxies identified so far. The source has a star-formation rate of 850 solar masses per year and is spatially resolved on scales of 5 kiloparsecs, with an implied dynamical mass of about 1.3?×?10(11) solar masses, a significant fraction of which is present in the form of molecular gas. Despite our accurate determination of redshift and position, a counterpart emitting starlight remains elusive.     

Bacterial RNA synthesis in frog auricles after intraperitoneal injection of bacteria

Résumé Des organes de plantes ou d'animaux mis dans une suspension bactérienne synthétisent du RNA bactérien. Ce phénomène que nous avons appelé transcession est dû au transfert de DNA spontanément cédé par les bactéries vivantes aux cellules des organismes supérieurs. Dans le présent travail, il est démontré que le même phénomène peut avoir lieu naturellement lorsqu'une grenouille est sujette à une infection bactérienne.

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We thank MissA. Cattaneo, MissJ. Henry for excellent technical assistance. This work was supported by a grant from the Fonds National Suisse de la Recherche Scientifique.     

Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome

Warburg Micro syndrome (WARBM1) is a severe autosomal recessive disorder characterized by developmental abnormalities of the eye and central nervous system and by microgenitalia. We identified homozygous inactivating mutations in RAB3GAP, encoding RAB3 GTPase activating protein, a key regulator of the Rab3 pathway implicated in exocytic release of neurotransmitters and hormones, in 12 families with Micro syndrome. We hypothesize that the underlying pathogenesis of Micro syndrome is a failure of exocytic release of ocular and neurodevelopmental trophic factors.     

Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations

Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N-glycosylation site in the IFNgammaR2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFNgamma. We then searched the Human Gene Mutation Database for potential gain-of-N-glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations ( approximately 1.4%) in 77 genes ( approximately 13.3%). Six mutant proteins bore new N-linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N-glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N-linked carbohydrate.     

Fitting a distance model to homogeneous subsets of variables: Points of view analysis of categorical data

An approach is presented for analyzing a heterogeneous set of categorical variables assumed to form a limited number of homogeneous subsets. The variables generate a particular set of proximities between the objects in the data matrix, and the objective of the analysis is to represent the objects in lowdimensional Euclidean spaces, where the distances approximate these proximities. A least squares loss function is minimized that involves three major components: a) the partitioning of the heterogeneous variables into homogeneous subsets; b) the optimal quantification of the categories of the variables, and c) the representation of the objects through multiple multidimensional scaling tasks performed simultaneously. An important aspect from an algorithmic point of view is in the use of majorization. The use of the procedure is demonstrated by a typical example of possible application, i.e., the analysis of categorical data obtained in a free-sort task. The results of points of view analysis are contrasted with a standard homogeneity analysis, and the stability is studied through a Jackknife analysis.