Evidence for Transcript Networks Composed of Chimeric RNAs in Human Cells

The classic organization of a gene structure has followed the Jacob and Monod bacterial gene model proposed more than 50 years ago. Since then, empirical determinations of the complexity of the transcriptomes found in yeast to human has blurred the definition and physical boundaries of genes. Using multiple analysis approaches we have characterized individual gene boundaries mapping on human chromosomes 21 and 22. Analyses of the locations of the 5′ and 3′ transcriptional termini of 492 protein coding genes revealed that for 85% of these genes the boundaries extend beyond the current annotated termini, most often connecting with exons of transcripts from other well annotated genes. The biological and evolutionary importance of these chimeric transcripts is underscored by (1) the non-random interconnections of genes involved, (2) the greater phylogenetic depth of the genes involved in many chimeric interactions, (3) the coordination of the expression of connected genes and (4) the close in vivo and three dimensional proximity of the genomic regions being transcribed and contributing to parts of the chimeric RNAs. The non-random nature of the connection of the genes involved suggest that chimeric transcripts should not be studied in isolation, but together, as an RNA network

Landscape of transcription in human cells

Eukaryotic cells make many types of primary and processed RNAs that are found either in specific sub-cellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic sub-cellular localizations are also poorly understood. Since 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, modifications 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 to a redefinition of the concept of a gene

Transcriptional coupling of distant regulatory genes in living embryos

International audienceThe prevailing view of metazoan gene regulation is that individual genes are independently regulated by their own dedicated sets of transcriptional enhancers. Past studies have reported long-range gene–gene associations1,2,3, but their functional importance in regulating transcription remains unclear. Here we used quantitative single-cell live imaging methods to provide a demonstration of co-dependent transcriptional dynamics of genes separated by large genomic distances in living Drosophila embryos. We find extensive physical and functional associations of distant paralogous genes, including co-regulation by shared enhancers and co-transcriptional initiation over distances of nearly 250 kilobases. Regulatory interconnectivity depends on promoter-proximal tethering elements, and perturbations in these elements uncouple transcription and alter the bursting dynamics of distant genes, suggesting a role of genome topology in the formation and stability of co-transcriptional hubs. Transcriptional coupling is detected throughout the fly genome and encompasses a broad spectrum of conserved developmental processes, suggesting a general strategy for long-range integration of gene activity

Intérêt de l’individualisation de l’alimentation des brebis laitières par l’utilisation d’un distributeur automatique de concentrés en salle de traite

National audienc

Chronic apelin treatment improves hepatic lipid metabolism in obese and insulin-resistant mice by an indirect mechanism

International audienc

Transient Hypermutagenesis Accelerates the Evolution of Legume Endosymbionts following Horizontal Gene Transfer

International audienceHorizontal gene transfer (HGT) is an important mode of adaptation and diversification of prokaryotes and eukaryotes and a major event underlying the emergence of bacterial pathogens and mutualists. Yet it remains unclear how complex phenotypic traits such as the ability to fix nitrogen with legumes have successfully spread over large phylogenetic distances. Here we show, using experimental evolution coupled with whole genome sequencing, that co-transfer of imuABC error-prone DNA polymerase genes with key symbiotic genes accelerates the evolution of a soil bacterium into a legume symbiont. Following introduction of the symbiotic plasmid of Cupriavidus taiwanensis, the Mimosa symbiont, into pathogenic Ralstonia solanacearum we challenged transconjugants to become Mimosa symbionts through serial plant-bacteria co-cultures. We demonstrate that a mutagenesis imuABC cassette encoded on the C. taiwanensis symbiotic plasmid triggered a transient hypermutability stage in R. solanacearum transconjugants that occurred before the cells entered the plant. The generated burst in genetic diversity accelerated symbiotic adaptation of the recipient genome under plant selection pressure, presumably by improving the exploration of the fitness landscape. Finally, we show that plasmid imuABC cassettes are over-represented in rhizobial lineages harboring symbiotic plasmids. Our findings shed light on a mechanism that may have facilitated the dissemination of symbiotic competency among a-and b-proteobacteria in natura and provide evidence for the positive role of environment-induced mutagenesis in the acquisition of a complex lifestyle trait. We speculate that co-transfer of complex phenotypic traits with mutagenesis determinants might frequently enhance the ecological success of HGT

ABRomics: A Galaxy-based one health antimicrobial resistance platform

International audienceAntibiotic resistance (ABR) is a major global public health issue designated for urgent action by international institutions, especially regarding the emergence and the global dissemination of multidrug-resistant bacteria (MDRB) and antibiotic resistance genes (ARGs) carried by mobile genetic elements. They are widely transmitted between humans, animals, and the environmental domains, without borders, calling for a One Health perspective on ABR. Whole genome sequencing (WGS) is used for molecular typing purposes at the highest resolution. It provides the genome sequences required for the identification of ARGs as well as mutations leading to a decrease in antibiotic susceptibility. Tracking transmissions of outbreaks and identifying sources of contamination is achievable with WGS data combined with epidemiological information. Ensuring the sharing of high-quality sequence data alongside interoperable curated metadata is a key requirement for understanding the spatiotemporal patterns of dissemination of MDRB and ARGs. Today, systematic genome sequencing and bioinformatics analyses partially address such major issues. However, the remaining major bottlenecks are data sharing and comparable results across multiple centers and labs. The ABRomics project aims to develop a secure One Health, online platform to make MDRB genomics, metagenomics data, and their metadata accessible to a network of researchers including epidemiologists, clinical microbiologists, and the wider research community. The ABRomics platform is a free, secure web-based (Django) service designed to facilitate collaboration between experts working on ABR. It offers a user-friendly interface for carrying out Galaxy-based bioinformatics analyses on both private and public sequencing data. It integrates project management functionalities so that users can store their biological sequence data and retrieve the results of launched analyses. ABRomics offers standardized Galaxy workflows to run ABR analyses of sequencing data from pathogenic strains (e.g. ARG detection, sequence typing, virulence factor detection, etc). These workflows have been submitted to Intergalactic Workflow Commission (IWC) and are documented with tutorials on the Galaxy Training Network. In ABRomics background, the UseGalaxy France server is used to schedule jobs via django-to-galaxy (a Django library to communicate with Galaxy API), allowing users to launch complex multi-step scientific workflows on the French Bioinformatics Institute (IFB) Core Cluster. The platform also offers an interface for cross-referencing and enriching results with other information and omics data. An Application Programming Interface (API) is available for integration with other systems, enabling the ABRomics platform to achieve interoperability. In this talk, we will present ABRomics, the secure multisectorial, open-access, online platform that analyzes (meta-)genomic data relating to ABR. We will also present the plans for the ABRomics platform to enable tracking of spatio-temporal dissemination of ABR from bacterial genomes and metagenomes, thereby improving surveillance and research in antimicrobial resistance