How do bacteria tune transcription termination efficiency?

Bacterial operons often contain intergenic transcription terminators that terminate some, but not all, RNA polymerase molecules. In these operons, the level of terminator readthrough determines downstream gene expression and helps establish protein ratios among co-regulated genes. Despite its critical role in maintaining stoichiometric gene expression, terminator strength remains difficult to predict from DNA sequence. The necessary features of a major class of bacterial terminators — intrinsic terminators — have been known for half a century, but a strong sequence–function model has yet to be developed. Here, we summarize high-throughput approaches for probing the sequence determinants of intrinsic termination efficiency and discuss the impact of trans-acting factors on this sequence–function relationship. Building on the main lessons from these studies, we map out the experimental challenges that must be circumvented to establish a quantitative model for termination efficiency.