Noncontiguous operon is a genetic organization for coordinating bacterial gene expression

Abstract

Bacterial 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.

Advances in bacterial transcriptome understanding: From overlapping transcription to the excludon concept

“…An extreme example of gene regulation by overlapping transcription has been recently described in S. aureus (Sáenz‐Lahoya et al, ) (Figure d). The new transcriptional organisation, termed ‘noncontiguous operon’, consists of operons that contain a gene(s) that is transcribed in the opposite direction to the rest of the genes of the operon.…”

“…On the other hand, RNA processing induces the stabilisation of the second half, including ytkD and MW1731 genes. Reduction in the levels of MenE and MenC proteins resulted in a slowed growth phenotype characteristic of small colony variants (SCVs) (Sáenz‐Lahoya et al, ).…”

“…The noncontiguous operon arrangement, including the menE‐menC‐MW1733‐ytkD‐MW1731 genes, may provide a mechanism to shut down the synthesis of menaquinone and the generation of SCVs under environmental conditions where the expression of MW1733 is highly induced (Sáenz‐Lahoya et al, ) (Figure ). The synthesis of menaquinone is accomplished by at least seven enzymes (MenA‐MenG) encoded in different operons (Hiratsuka et al, ).…”

“…Interestingly, a second noncontiguous operon configuration is found among men genes. Specifically, MW0924 is co‐transcribed with menFDHB genes forming a long polycistronic transcript that overlaps the menA mRNA, which is encoded between MW0924 and menF in the opposite direction (Sáenz‐Lahoya et al, ). It is tempting to speculate that both antisense transcripts will also be mutually regulated expanding the regulatory options to generate SCVs and normal‐growing bacteria depending on appropriate environmental signals.…”

“…Examples of excludon transcriptional organisation have been described in different bacteria(Georg & Hess, 2018;Lasa et al, 2011;Lioliou et al, 2012;Quereda & Cossart, 2017;Sáenz-Lahoya et al, 2019) (Figure 3). However, the exact mechanisms underlying the inhibitory effect of the overlapped transcripts in excludon organisation have just recently started being clarified.An extreme example of gene regulation by overlapping transcription has been recently described in S. aureus(Sáenz-Lahoya et al, 2019) (Figure 3d). The new transcriptional organisation, termed 'noncontiguous operon', consists of operons that contain a gene(s) that is transcribed in the opposite direction to the rest of the genes of the operon.…”