Antisense RNA, Transcriptional Interference and Genetic Switch: Train Wreck or Noise Filter?

Convergent overlapping genes with face to face promoters expressing cis sense-antisense transcripts

(SAT) from the opposite strands of DNA are commonly seen in prokaryotic and eukaryotic genomes.

The expression of these gene pairs is often reciprocally regulated through transcriptional interference

(TI); a mechanism by which elongating RNA polymerases, like trains approaching from opposite

directions, collide with each other. The wreckage caused by such collisions inevitably includes aborted

RNA. Increasing evidence indicates that TI represents a unique mechanism in gene expression

regulation. Many such systems are involved in controlling key biological events including the subjects of

our study: prgX/prgQ gene pair in Enterococcus faecalis controlling the initiation of conjugation process

transferring antibiotic resistance plasmid, and the scbA/scbR gene pair in Streptomyces coelicolor

controlling the onset of antibiotic production. To understand this regulatory mechanism, a discrete

mathematical model was developed to quantitatively assess the effect of RNA polymerase collision on

transcription of the gene pair. Our model demonstrates that TI can give rise to a “switch-like” behavior,

whereby depending on the state of the two promoters the system could switch between two distinct

outcomes. The aborted transcripts produced by transcriptional interference in convergent promoter

systems can potentially interact with opposing transcripts via sense/antisense interaction. Our data

indicates that the aborted transcripts exist in various sizes depending on the loci of collision.

Incorporating sense-antisense interaction between full length sense transcripts and aborted antisense

transcripts in the model we demonstrate that aborted transcripts dampen the noise in such gene pairing

systems, thus making such a switch behavior more robust. Given that sense/antisense pairs are conserved

across species, TI is likely to have a significant regulatory role in gene expression. Our model suggests

that they have the functionality to be gene switches.

Keywords: Transcriptional interference, Sense antisense transcripts, Antisense regulation,

Convergent promoters, RNA polymerase collision, Mathematical model