A quantitative comparison of sRNA-based and protein-based gene regulation

Small, non-coding RNAs (sRNAs) play important roles as genetic regulators in prokaryotes. sRNAs act post-transcriptionally via complementary pairing with target mRNAs to regulate protein expression. We use a quantitative approach to compare and contrast sRNAs with conventional transcription factors (TFs) to better understand the advantages of each form of regulation. In particular, we calculate the steady-state behavior, noise properties, frequency-dependent gain (amplification), and dynamical response to large input signals of both forms of regulation. While the mean steady-state behavior of sRNA-regulated proteins exhibits a distinctive tunable threshold-linear behavior, our analysis shows that transcriptional bursting leads to significantly higher intrinsic noise in sRNA-based regulation than in TF-based regulation in a large range of expression levels and limits the ability of sRNAs to perform quantitative signaling. Nonetheless, we find that sRNAs are better than TFs at filtering noise in input signals. Additionally, we find that sRNAs allow cells to respond rapidly to large changes in input signals. These features suggest a niche for sRNAs in allowing cells to transition quickly yet reliably between distinct states. This functional niche is consistent with the widespread appearance of sRNAs in stress-response and quasi-developmental networks in prokaryotes.