Abstract
cis-encoded antisense RNAs (cis asRNA) have been reported to participate in gene expression regulation in both eukaryotic and prokaryotic organisms. Its presence in Streptomyces coelicolor has also been reported recently; however, its role has yet to be fully investigated. Using mathematical modeling we explore the role of cis asRNA produced as a result of convergent transcription in scbA-scbR genetic switch. scbA and scbR gene pair, encoding repressor–amplifier proteins respectively, mediates the synthesis of a signaling molecule, the γ-butyrolactone SCB1 and controls the onset of antibiotic production. Our model considers that transcriptional interference caused by convergent transcription of two opposing RNA polymerases results in fatal collision and transcriptional termination, which suppresses transcription efficiency. Additionally, convergent transcription causes sense and antisense interactions between complementary sequences from opposing strands, rendering the full length transcript inaccessible for translation. We evaluated the role of transcriptional interference and the antisense effect conferred by convergent transcription on the behavior of scbA-scbR system. Stability analysis showed that while transcriptional interference affects the system, it is asRNA that confers scbA-scbR system the characteristics of a bistable switch in response to the signaling molecule SCB1. With its critical role of regulating the onset of antibiotic synthesis the bistable behavior offers this two gene system the needed robustness to be a genetic switch. The convergent two gene system with potential of transcriptional interference is a frequent feature in various genomes. The possibility of asRNA regulation in other such gene-pairs is yet to be examined.
Highlights
Transcription from a pair of promoters arranged in face-to-face orientation is ubiquitous both in bacteria and eukaryotes
Our model incorporates three mechanisms of transcriptional interference, namely, (i) promoter occlusion, in which a passing RNA polymerases (RNAPs) originating at pR blocks access to pA and vice versa, (ii) collision between converging elongating RNAP originating from pA and pR and (iii) sitting duck collisions, in which closed promoter complex at pA is removed by collision with a passing RNAP originating at pR and vice versa [34,40]
It is assumed that the 39 end-most base of a nascent transcript is 20 bp from the locus of the front end of RNAP (RNAP footprint), and this is used to calculate the length of a truncated RNA due to aborted transcription [40]
Summary
Transcription from a pair of promoters arranged in face-to-face orientation is ubiquitous both in bacteria and eukaryotes It leads to a complete or partial overlap between convergent or divergent transcripts. Widespread convergent transcription leads to a large number of cis asRNA in eukaryotic genomes including human [1], mouse [2], Drosophila [3], A. thaliana [4], and yeast [5]. Many of these cis asRNA’s are non-coding, but have been shown to participate in regulation [2,6,7]. The role of convergent transcription in the scbA-scbR system is evaluated
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