(Oxford University Press, 2024) Iturbe Sanz, Pablo; San Martín Bernal, Álvaro; Hamamoto, Hiroshi; Marcet Houben, Marina; Galbaldón, Toni; Solano Goñi, Cristina; Lasa Uzcudun, Íñigo; Ciencias de la Salud; Osasun Zientziak; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
Bacteria synchronize the expression of genes with related functions by organizing genes into operons so that they are cotranscribed
together in a single polycistronic messenger RNA. However, some cellular processes may benefit if the simultaneous production of the
operon proteins coincides with the inhibition of the expression of an antagonist gene. To coordinate such situations, bacteria have
evolved noncontiguous operons (NcOs), a subtype of operons that contain one or more genes that are transcribed in the opposite
direction to the other operon genes. This structure results in overlapping transcripts whose expression is mutually repressed. The
presence of NcOs cannot be predicted computationally and their identification requires a detailed knowledge of the bacterial transcriptome. In this study, we used direct RNA sequencing methodology to determine the NcOs map in the Staphylococcus aureus genome.
We detected the presence of 18 NcOs in the genome of S. aureus and four in the genome of the lysogenic prophage 80α. The identified
NcOs comprise genes involved in energy metabolism, metal acquisition and transport, toxin–antitoxin systems, and control of the
phage life cycle. Using the menaquinone operon as a proof of concept, we show that disarrangement of the NcO architecture results
in a reduction of bacterial fitness due to an increase in menaquinone levels and a decrease in the rate of oxygen consumption. Our
study demonstrates the significance of NcO structures in bacterial physiology and emphasizes the importance of combining operon
maps with transcriptomic data to uncover previously unnoticed functional relationships between neighbouring genes.
