Stage & emploi

Pervasive transcription, whereby transcripts get spuriously generated from all over the genome, often in-antisense to functional genes, is a universal and ambivalent property of living systems. Antisense transcription can be undesirable and even dangerous as it contributes to gene expression noise and may lead to genome instability. But it also conceals an inexhaustible source of evolutionary innovation, from which new functional RNAs and regulatory circuits can arise. Two conserved RNA-binding proteins (RBPs), transcription termination factor Rho and double-stranded RNA-specific RNase III, function at co- and post-transcriptional levels to restrain pervasive transcription and even "adopt" some of the resulting RNAs for regulatory purposes in bacteria. Therefore, these RBPs are potentially important evolutionary factors that, by "managing" the transcriptome, hold keys to bacterial adaptation and long-term success. To understand the evolutionary significance of pervasive antisense transcription and of the RBPs that control it, we will perform large-scale laboratory evolution experiments involving two phylogenetically and ecologically distant bacteria, a human commensal Escherichia coli and the pathogen Staphylococcus aureus. We will see how both bacteria, deprived of Rho or RNase III, adapt, under various conditions, to unleashed pervasive transcription and other unique gene expression challenges caused by this handicap. Leveraging the complementary expertise of both laboratories in RNA biology of Gram-positive and Gram-negative bacteria, using genomic, transcriptomic, genetic, biochemical, and physiological approaches, we will address, in a comparative and synthetic way, the underlying molecular mechanisms and the adaptive rationale of the observed evolutionary events.