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Abstract
Pausing by RNA polymerase (RNAP) during transcription regulates gene expression in
all domains of life. In this review, we recap the history of transcriptional pausing
discovery, summarize advances in our understanding of the underlying causes of pausing
since then, and describe new insights into the pausing mechanisms and pause modulation
by transcription factors gained from structural and biochemical experiments. The accumulated
evidence to date suggests that upon encountering a pause signal in the nucleic-acid
sequence being transcribed, RNAP rearranges into an elemental, catalytically inactive
conformer unable to load NTP substrate. The conformation, and as a consequence lifetime,
of an elemental paused RNAP is modulated by backtracking, nascent RNA structure, binding
of transcription regulators, or a combination of these mechanisms. We conclude the
review by outlining open questions and directions for future research in the field
of transcriptional pausing.