Sáenz Lahoya, S.Bitarte Manzanal, NereaGarcía, BeñatBurgui Erice, SaioaVergara Irigaray, MartaValle Turrillas, JaioneSolano Goñi, CristinaToledo Arana, AlejandroLasa Uzcudun, Íñigo2020-01-072020-01-0720190027-842410.1073/pnas.1812746116https://academica-e.unavarra.es/handle/2454/36000Bacterial genes are typically grouped into operons defined as clusters of adjacent genes encoding for proteins that fill related roles and are transcribed into a single polycistronic mRNA molecule. This simple organization provides an efficient mechanism to coordinate the expression of neighboring genes and is at the basis of gene regulation in bacteria. Here, we report the existence of a higher level of organization in operon structure that we named noncontiguous operon and consists in an operon containing a gene(s) that is transcribed in the opposite direction to the rest of the operon. This transcriptional architecture is exemplified by the genes menE-menC-MW1733-ytkD-MW1731 involved in menaquinone synthesis in the major human pathogen Staphylococcus aureus. We show that menE-menC-ytkD-MW1731 genes are transcribed as a single transcription unit, whereas the MW1733 gene, located between menC and ytkD, is transcribed in the opposite direction. This genomic organization generates overlapping transcripts whose expression is mutually regulated by transcriptional interference and RNase III processing at the overlapping region. In light of our results, the canonical view of operon structure should be revisited by including this operon arrangement in which cotranscription and overlapping transcription are combined to coordinate functionally related gene expression.6 p.application/pdfengOperonAntisense transcriptionOverlapping transcriptionRNase IIIMenaquinoneinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccess