title: Convergent transcription in the butyrolactone regulon in Streptomyces coelicolor confers a bistable genetic switch for antibiotic biosynthesis.
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.
authors.affiliation: Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Anushree
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Laurie
authors.initials: L
authors.lastname: Drews
authors.forename: Sarika
authors.initials: S
authors.lastname: Mehra
authors.forename: Eriko
authors.initials: E
authors.lastname: Takano
authors.forename: Yiannis N
authors.initials: YN
authors.lastname: Kaznessis
authors.forename: Wei-Shou
authors.initials: WS
authors.lastname: Hu
mesh_terms: D015107:4-Butyrolactone / Q000235:genetics*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001483:Base Sequence; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D053263:Gene Regulatory Networks / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics*; D005812:Genes, Switch / Q000235:genetics*; D056426:Genetic Loci; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic / Q000235:genetics; D016372:RNA, Antisense / Q000737:chemistry / Q000235:genetics; D018085:Regulon / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism; D048372:Streptomyces coelicolor / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D016372:RNA, Antisense; D012097:Repressor Proteins; D012321:DNA-Directed RNA Polymerases; D015107:4-Butyrolactone