# Small RNA driven feed-forward loop: critical role of sRNA in noise filtering

## TL;DR

This study analyzes a novel sRNA-driven feed-forward loop in Salmonella, revealing its superior response speed, sensitivity, and noise filtering capabilities compared to traditional gene regulation motifs, highlighting the critical role of sRNA.

## Contribution

It provides the first rigorous quantitative and stochastic analysis of the sRNA-driven FFL, demonstrating its enhanced response and noise filtering properties over transcriptional FFLs.

## Key findings

- sFFL exhibits stronger, faster, and more sensitive responses.
- Optimal noise filtration depends on sRNA synthesis and activator degradation rates.
- sRNA is crucial for rapid, reliable, and noise-resistant gene regulation.

## Abstract

A feed-forward loop (FFL) is a common gene-regulatory motif in which usually the upstream regulator is a protein, a transcription factor, that regulates the expression of the target protein in two parallel pathways. Here, we study a distinct sRNA-driven FFL (sFFL) discovered recently in Salmonella enterica. Unlike previously studied transcriptional FFLs (tFFL) and sRNA-mediated FFLs (smFFL), here the upstream regulator is an sRNA that activates the target protein and its transcriptional activator. Such sFFL has not been subjected to rigorous analysis. We, therefore, set out to understand two aspects. First is a quantitative comparison of the regulatory response of sFFL with tFFL and smFFL using a differential equation framework. Since the process of gene expression is inherently stochastic, the second objective is to find how the noise affects the functionality of sFFL. We find the response of sFFLto be stronger, faster, and more sensitive to the initial concentration of the upstream regulator than tFFL and smFFL. Further, a generating function based analysis and stochastic simulations lead to a non-trivial prediction that an optimal noise filtration can be attained depending on the synthesis rate of the sRNA and the degradation rate of the transcriptional activator. We conclude that in sFFL, sRNA plays a critical role not only in driving a rapid and strong response, but also a reliable response that depends critically on its concentration. Given the advantages of sFFL brought out in this work, it should not be surprising if future work reveals their employment in different biological contexts.