| Description |
Newly discovered, noncoding RNA regulate cellular processes and gene expression. Simple model systems, such as quorum sensing systems, are studied to understand the mechanisms by which these RNA act on their targets. Quorum sensing is a process by which bacteria coordinate expression of their genes based on the local cell-population density. Up to five noncoding RNA, called small RNA (sRNA), in the quorum sensing systems of Vibrio harveyi and Vibrio cholerae regulate expression of the master transcriptional regulator, LuxR (V. harveyi ) and HapR (V. cholerae). LuxR/HapR regulate genes associated with virulence and bioluminescence that are downstream of the quorum sensing system. The V. harveyi and V. cholerae quorum sensing systems are topologically identical and their components are homologous, yet each responds differently under identical experimental conditions. Experiments show that all sRNA are necessary in V. harveyi and any single sRNA is sufficient in V. cholerae to repress bioluminescence. Hence, Qrr are additive in V. harveyi and redundant in V. cholerae. Subsequent experiments have shown that feedback in the sRNA circuit increases the expression of Qrr when one or more Qrr are removed. Differences in the tuning of this feedback are thought to cause the additive and redundant Qrr phenotypes; however, this long-standing hypothesis remains untested. In this work, a novel model of the V. harveyi and V. cholerae sRNA circuit is formulated and parameterized to identify parametric differences underlying the phenotypic differences. This yields a single model with two different parameterizations whose behavior agrees quantitatively with a variety of empirical data from V. harveyi and V. cholerae. The model, therefore, can be used for the in silico design, testing, and analysis of experiments and, as such, is a utility to generate experimentally verifiable hypotheses. Analysis of the model shows that the feedback in the sRNA circuit is neither necessary nor sufficient to explain the phenotypic differences, which is in contrast to the long-standing hypothesis. Rather, the additive and redundant Qrr phenotypes are emergent phenomena and, in the case of V. harveyi and V. cholerae, reflect differences in the saturation of the protein chaperon Hfq with sRNA. Overall, this suggests that Hfq is an important modulator of sRNA-facilitated repression of target mRNA. |
