convergent transcription in the butyrolactone regulon in streptomyces coelicolor confers a bistable genetic switch for antibiotic biosynthesis收敛丁内酯的转录调节子在链霉菌属coelicolor授予抗生素生物合成的双稳态基因开关.pdfVIP

Convergent Transcription in the Butyrolactone Regulon in Streptomyces coelicolor Confers a Bistable Genetic Switch for Antibiotic Biosynthesis 1 1 2 3 1 Anushree Chatterjee , Laurie Drews , Sarika Mehra , Eriko Takano , Yiannis N. Kaznessis , Wei-Shou Hu1* 1 Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota, United States of America, 2 Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, India, 3 Department of Microbial Physiology, University of Groningen, Groningen, The Netherlands 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 c-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 t