Kinetic modeling reveals additional regulation at co-transcriptional level by post-transcriptional sRNA regulators

Small RNAs (sRNAs) are important gene regulators in bacteria. Many sRNAs act post-transcriptionally by affecting translation and degradation of the target mRNAs upon base-pairing interactions. Here we present a general approach combining imaging and mathematical modeling to determine kinetic parameters at different levels of sRNA-mediated gene regulation that contribute to overall regulation efficacy. Our data reveal that certain sRNAs previously characterized as post-transcriptional regulators can regulate some targets co-transcriptionally, leading to a revised model that sRNA-mediated regulation can occur early in an mRNA's lifetime, as soon as the sRNA binding site is transcribed. This co-transcriptional regulation is likely mediated by Rho-dependent termination when transcription-coupled translation is reduced upon sRNA binding. Our data also reveal several important kinetic steps that contribute to the differential regulation of mRNA targets by an sRNA. Particularly, binding of sRNA to the target mRNA may dictate the regulation hierarchy observed within an sRNA regulon.

Automated summary

Small RNAs (sRNAs) are important gene regulators in bacteria, acting post-transcriptionally by affecting translation and degradation of target mRNAs. Some sRNAs can regulate targets co-transcriptionally early in an mRNA's lifetime, potentially mediated by Rho-dependent termination. Data also reveals that certain kinetic steps and sRNA binding to target mRNA may dictate the regulation hierarchy within sRNA regulons.