期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：50
页码：E6835-E6843
DOI：10.1073/pnas.1515383112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceTranscription factors typically bind to more sites than are functionally affected upon transcription factor inactivation. What, then, determines whether transcription factor binding impacts gene expression? Here we address this question by investigating Rho, the essential transcription termination factor that associates with most newly transcribed RNAs in bacteria, but promotes transcription termination only in a fraction of these transcripts. We uncover a novel RNA element that sequesters Rho in an inactive complex, thereby advancing transcription without affecting Rho binding. Our results indicate that the site of action of transcription factors is defined not only by sequences that mediate their recruitment but also by sequences that antagonize their activity. The transcription termination factor Rho associates with most nascent bacterial RNAs as they emerge from RNA polymerase. However, pharmacological inhibition of Rho derepresses only a small fraction of these transcripts. What, then, determines the specificity of Rho-dependent transcription termination? We now report the identification of a Rho-antagonizing RNA element (RARE) that hinders Rho-dependent transcription termination. We establish that RARE traps Rho in an inactive complex but does not prevent Rho binding to its recruitment sites. Although translating ribosomes normally block Rho access to an mRNA, inefficient translation of an open reading frame in the leader region of the Salmonella mgtCBR operon actually enables transcription of its associated coding region by favoring an RNA conformation that sequesters RARE. The discovery of an RNA element that inactivates Rho signifies that the specificity of nucleic-acid binding proteins is defined not only by the sequences that recruit these proteins but also by sequences that antagonize their activity.
