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Dynamic competition between a ligand and transcription factor NusA governs riboswitch-mediated transcription regulation

2021/10/14 by Adrien Chauvier, Chauvier, Adrien, Pujan Ajmera +5
Biochemistry, Genetics and Molecular Biology · #Chemistry #Co-transcriptional folding #NusA #RNA Research and Splicing #RNA and protein synthesis mechanisms #RNA modifications and cancer #RNA polymerase pausing #Science #riboswitch #single molecule fluorescence microscopy

paper · doi:10.7302/3356

openalex publication_date 2021/10/14 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/01

Abstract

Co-transcriptional RNA folding is widely assumed to influence the timely control of gene expression, but our understanding remains limited. In bacteria, the fluoride (F-) sensing riboswitch is a transcriptional control element essential to defend against toxic F- levels. Using this model riboswitch, we find that its ligand F- and essential bacterial transcription factor NusA compete for binding the co-transcriptionally folding RNA, opposing each other’s modulation of downstream pausing and termination by RNA polymerase. Single molecule fluorescence assays probing active transcription elongation complexes discover that NusA unexpectedly binds highly reversibly, frequently interrogating the complex for emerging, co-transcriptionally folding RNA duplexes. NusA thus fine-tunes the transcription rate in dependence of the ligand-responsive higher order structure of the riboswitch. At the high NusA concentrations found intracellularly, this dynamic modulation is expected to lead to adaptive bacterial transcription regulation with fast response times.

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