Comparative transcriptomics of pathogenic and non-pathogenic Listeria species

Listeria monocytogenes is a human pathogen responsible for food-borne infections. Previous genomic comparisons between L. monocytogenes and Listeria innocua, a closely related non-pathogenic species, were pivotal in identification of protein coding genes essential for virulence. To date however, no such comparison has focused on the non-coding genome, although several small RNAs play important roles in Listeria virulence. We used massive strand-specific cDNA sequencing to produce genome-wide transcription start site (TSS) maps for both organisms, and developed an integrative browser to study both transcriptomes at a single-base resolution. Our data reveal a remarkable conservation across the vast majority of transcripts, but also significant divergence in a subset of cis- and trans- acting non coding RNAs, possibly leading to different regulatory outcomes between the species. Remarkably, our results suggest a novel, recurring and conserved form of regulation by long cis-encoded antisense transcripts (lasRNAs), where the lasRNA overlapping one gene also serves as the 5' UTR of the adjacent gene encoded on the reverse orientation. Pairs of divergent genes having such lasRNA/5' UTR organization encode proteins with opposing or mutually exclusive functions, suggesting a mechanism whereby a lasRNA represses one gene while simultaneously activating another. We named the structure an "excludon".
Citation: Wurtzel et al. Molecular Systems Biology, 8:583 (2012).