Theoretical Analysis of Catalytic-sRNA-Mediated Gene Silencing

Small regulatory RNA (sRNA) that acts by an antisense mechanism is critical for gene regulation at the posttranscriptional level. Recently, an Hfq-dependent sRNA named MicM, which is related to the regulation of outer membrane protein, was verified as a novel antisense sRNA due to its catalytic mode of regulation. Here we propose a simple kinetic model for the enzyme-like regulation mode of sRNA and study in detail the noise properties of the target gene under various recycling rates of the regulator. We predict that the recycling rate of sRNA and other relative parameters have significant influence on the noise strength of target expression. In comparison with the stoichiometric regulatory mode, a lesser fluctuation of target expression was observed near the threshold at which the transcription rates of both sRNA and target mRNA equal each other. We also found that the new mode is better in terms of rapid response to external signals. However, it needs more time to achieve target recovery if the stimulating signal disappears. Additionally, the obtained time evolution results of the MicM–ybfM interaction system based on our model are consistent with previous experimental results, serving as experimental evidence to back up our theoretical analysis.

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► This study proposes a theoretical model for catalytic-sRNA-mediated gene silencing.
► This study extrapolates between stoichiometric limits and catalytic limits using a single parameter.
► Recycling greatly increases the efficiency of sRNA.
► Recycling significantly attenuates transcriptional noise.
► Recycling of sRNA increases the rapidity of response.