Sedlyarova Nadezda, Shamovsky Ilya, Bharati Binod K, Epshtein Vitaly, Chen Jiandong, Gottesman Susan, Schroeder Renée, Nudler Evgeny
Department of Biochemistry and Cellbiology, Max F. Perutz Laboratories, University of Vienna, Dr. Bohrgasse 9/5, 1030 Vienna, Austria; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
Cell. 2016 Sep 22;167(1):111-121.e13. doi: 10.1016/j.cell.2016.09.004.
Bacterial small RNAs (sRNAs) have been implicated in various aspects of post-transcriptional gene regulation. Here, we demonstrate that sRNAs also act at the level of transcription termination. We use the rpoS gene, which encodes a general stress sigma factor σ(S), as a model system, and show that sRNAs DsrA, ArcZ, and RprA bind the rpoS 5'UTR to suppress premature Rho-dependent transcription termination, both in vitro and in vivo. sRNA-mediated antitermination markedly stimulates transcription of rpoS during the transition to the stationary phase of growth, thereby facilitating a rapid adjustment of bacteria to global metabolic changes. Next generation RNA sequencing and bioinformatic analysis indicate that Rho functions as a global "attenuator" of transcription, acting at the 5'UTR of hundreds of bacterial genes, and that its suppression by sRNAs is a widespread mode of bacterial gene regulation.
细菌小RNA(sRNA)已被证明参与转录后基因调控的各个方面。在此,我们证明sRNA也在转录终止水平发挥作用。我们使用编码一般应激σ因子σ(S)的rpoS基因作为模型系统,表明sRNA DsrA、ArcZ和RprA在体外和体内均结合rpoS 5'非翻译区(UTR)以抑制依赖Rho的过早转录终止。在生长进入稳定期的转变过程中,sRNA介导的抗终止作用显著刺激rpoS的转录,从而促进细菌对整体代谢变化的快速适应。新一代RNA测序和生物信息学分析表明,Rho作为转录的全局“衰减子”,作用于数百个细菌基因的5'UTR,并且sRNA对其的抑制是细菌基因调控的一种广泛模式。